Effects of intense noise on the fetal sheep auditory mechanism as assessed by auditory brainstem response and cochlear h...

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Title:
Effects of intense noise on the fetal sheep auditory mechanism as assessed by auditory brainstem response and cochlear histology
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xv, 158 leaves : ill., photographs ; 29 cm.
Language:
English
Creator:
Pierson, Linda Louise
Publication Date:

Subjects

Subjects / Keywords:
Ewes -- Fetuses -- Effect of noise on   ( lcsh )
Auditory perception   ( lcsh )
Genre:
bibliography   ( marcgt )
theses   ( marcgt )
non-fiction   ( marcgt )

Notes

Thesis:
Thesis (Ph. D.)--University of Florida, 1993.
Bibliography:
Includes bibliographical references (leaves 110-119).
General Note:
Typescript.
General Note:
Vita.
Statement of Responsibility:
by Linda Louise Pierson.

Record Information

Source Institution:
University of Florida
Rights Management:
All applicable rights reserved by the source institution and holding location.
Resource Identifier:
aleph - 001947402
notis - AKC3724
oclc - 31143078
System ID:
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Full Text











EFFECTS OF INTENSE NOISE ON THE FETAL SHEEP AUDITORY
MECHANISM AS ASSESSED BY AUDITORY BRAINSTEM
RESPONSE AND COCHLEAR HISTOLOGY












By


LINDA


LOUISE


PIERSON


A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY


UNIVERSITY


OF FLORIDA






























Copyright


1993


Linda


Louise


Pierson


























Dedi


James


cated


. Pierson


a renaissance


best


man


friend















ACKNOWLEDGMENTS


words


on the


bumper


icker


on the


car


in front


me said,


ect a miracle.


time,


thought


miracle


might


be nice,


now


realize


that


entire


life,


people


have


that


been


have


surrounded


known.


miracles


direct


form


thanks


acknowledgment


to the


following


people


organizations


who


, knowingly


or not,


have


served


in supporting


successful


completion


United


States


this


Army


task


acknowledged


ass


instance


that


has made


this


experience


possible.


Many


military


civilian


individuals


whom


through


my Army


career


have


shaped


me.


only


did


Amy


Donahue


teach


me to


think


about


ear


hearing


new


different


ways


, but


she also


cheerfully


suff


ered


through


each


minor


academic


or research


setback.


Perhaps


now,


will


phone


when


things


are


going


well.


Lieutenant


Colonel


Dean


Harmer


encouraged


me to apply


to the


Army


s program


funding


doctoral


cation.


He planted


an idea


that


never


would


have


occurred


me on my


own.


Many


years


ago,


Major


Nancy


Vause


taught


me how


organization


to getting


1 a rno


mrnr11 nn


nf :tt rlr


rlnno


I rl


1 mn toA


amrntniin n


i m o-


b








taught


me almost


everything


know


about


hearing


cons


ervation


encouraged


me to


try


new


and


different


projects


Finally


, Colonel


Rodney


Atack,


a true


leader


mentor


and


a good


man,


ves


everyone


foundation


to live


up to the Army'


motto


can


As a major


part


academic


experience


, the


committee

knowledge


members


have


experience


ability


to the


proc


to contribute


ess.


their


am thankful


have


a group


so willing


give


freely


themselves


Emmett


Bolch


agreed


serve


on this


committee


whose


focus


became


rather


removed


from


basic


engineering


. Alice


Holmes


provided


one


best


course


work


experiences


and


made


me realize


that


might


clinical


audiology


and


hearing


aid


fittings


after


all.


The


intell


ectual


exchange


between


. Scott


Griffiths


me has


greatly


benefitted


me.


was


never


afraid


of difficult


questions


, the


ones


that


no one


answers


to yet.


remaining


three


committee


members


exhibited


super


-human


patience


Dr. Kyle


Rarey


refrained


from


laughing


when


revealed


lack


talent


at cochlear


surface


preparation


that


I had


labeled


"kibbl


earn


bits


about


thank


cochlea


him


first-hand.


allowing


The


me to


more


see


learn


and


about


structure,


more


am amaz


. Robert


Abrams


had


the


ability


to restrain


himself


in surgery


many


times


when


he would


have


liked


to have


taken


over


He also


had


the


Dr








demonstrated


a great respect for research animals.


taught me

assured by


that

his


"Research


takes many forms.


former students


that Dr.


I had been


Ken Gerhardt,


committee chairman,


would be a


wonderful mentor.


He lived


to his


reputation.


He was always willing to entertain my


questions


even


same question


two or three


times.


understood


the Army requirements and


facilitated my


academic


research achievements.


Not everything


learned at a


university


comes


from the


professors.


Isabelle Williams


knows her way


around a


lab and an operating room and


is capable of


accomplishing


just about anything


she decides to do.


Like Dr.


Abrams,


a great respect


for the research animals.


Pauletta


Sanders


forgotten more about histology than


will


ever


know.


serial


taught me


the practical hints


celloidin sections and


I knew


in the method


learned something


when she


said,


"These sections


look


like mine.


Because our


families are where we are


born


, grow up


spend most


of all.

when a


always


of our time and die,


My parents,

person works


been proud


their


Evelyn and Ray


hard,


impact


Dorn,


she can achieve.


of her nursing


school


is the greatest


taught me that

My mother has


achievements and her


pursuit

wishes.


of higher


father


education


that was against her parent's


especially touched me when he was


very


ill,


insistent


that


choose


the best


possible








Andrew


Pierson


anything


They


always seem

provide the


to believe

sunshine


that

in my


their

life


mom

and


can

are


do

my


greatest


treasures.


Finally


, my


husband


James


Pierson


always


provided


right


amount


of encouragement


the


right


time.


He helped


me with


more


things


than


can


remember


acousti


Providing


, and


help


drafting


in stati


one


, neuroscience


figures


dissertation


are


just


a few


of his


good


deeds


I cherish


our


marriage


thank


him


being


best


friend.















TABLE


OF CONTENTS


Page


AC KNOWLE DGMENTS


LIST

LIST


OF TABLES

OF FIGURES


ABSTRACT


. . .


. . . S S


. S S S


xiii


CHAPTER


INTRODUCTION


S S S . 1l


se-


Induced


Asses
Cochi


sment
ear C


Hearing


of NIHL
changes.


Loss


Damage


Fetal


Hearing.


. . . 12


eve


lopment.


Assessment
Function.


of Fetal


Audit


. . 20


OBJECTIVES


AND


METHODS


. . . 26


Subj
Proc


ects. .
edures.


Surgery
The ABR


The Noise
Histologic


Exposure
al Method


Design.


Experiment
Experiment


One
Two













III.


RESULTS


DISCUSSION


Subjects.
Nonexposed


. . . . 44


Subj


ects


. . 45


Normal


ABR


Devel


opment


. . 45


Description


Normal


Cochl


eae


Experiment


One.


. 67


Deve


lopmental


Effect


on the


ABR.


Experiment


Two.


. . . 78


Early
Effe


Cochlear


Versus


Late


on the


Compari


Exposure
ABR . .


son


Nonexposed


Subj


ects.


S . 90


Noi


se-Exposed


Subj


SUMMARY


AND


CONCLUSIONS


Nonexposed


ABR


Cyt


ococ


eogram


Noise
Impli


-Expos
cation


ABR


s for


and
Rese


ococ


eogram


arch


REFERENCES

APPENDIX.


BIOGRAPHICAL


.*... .


SKETCH


Page

















LIST


OF TABLES


Experiment

Experiment


Timeline

Timeline


.O .. ..

. I. .


Attained


diff


p-values
erences.


click


-evo


ency


. . S S .


Page















LIST


OF FIGURES


Time


waveforms


rec


orded


ectra


with


an accel


ABR


eromet


stimuli


er.


3-1.


ck-evoked


NHL


over


ABR


from


waveforms


subject


increasing


recorded


number


1018


. 46


3-2.


Mean


ABR


thresholds


tone


nonexpo


bursts


sed fetu


to clicks
recorded


ses.


ero


from


3-3.


Mean


ABR


late


ncy-inten


sity


functions


dGA


nonexpo


sed fetu


ses.


3-4.


Various


Waves


s mean
, II,


ens


ities


nonexposed


clic


IV lat


k-evoked


encies


3-5.


Photograph
right


the
from


bony
a 4


labyrinth


to 5


week


lamb


3-6.


Cros


s-sec


tional


view


superior


view


the
cell


organ
oidin


Subject


Corti


section


on the
obtained


same
from


1011.


Magnification
of Corti


of
seen


aspects


same


organ


serial


colloidin


section


a . . 63


Cochlear


recons


truction


left


ear


Subject
animal


1006N,


that


dGA


was


ins


nonexpos


trumented


ABR


0 0 0 . .


3-9.


Mean


ABR


early


there
exp


sholds


ose


d animal


nonexpo
various


sed and
s GAs.


3-10.


Mean


thrsfhnli


di ff


ronr oc


hot+TaOO


TI


a r 1 ?


. . 50


. . 0 56


Page


i









Page


Mean


ABR


thresholds


stimuli


dGA


. . . . 73


Mean


ABR


click


-evoked


encies


nHL


various


. . 76


Mean


pre-
thres
noise
noise


and
holds
-expo
-expo


post-exposure


for
sed
sed


the
(113
(130


nonexpos


dGA)
dGA)


rec
ed,


very
early


late


groups.


Mean


ck-evoked


minus


early


Cytocochi


dGA
late


eograms


latency


differs


nonexpo


noise


from


-expos


groups


dGA
sed


ed animal


subjects


in thi


study


S. . 93















Abstract


of Dissertation


Presented


Graduate


School


the University
Requirements f


EFFECTS


OF INTENSE


MECHANISM


RESPONSE


Florida


Degree


NOISE


3SESSED
AND CC


in Partial


Doctor


FETAL


ON THE


BY AUDITORY


CLEARR


Fulfillment


of Philo


SHEEP AU


sophy


DITORY


BRAINSTEM


HISTOLOGY


Linda


Louise


Pierson


August


1993


Chairman:


Kenneth


Gerhardt


Major


Department:


Communication


Processes


Disorders


auditory


brainstem


response


was


recorded


from


utero


fetal


sheep


from


days


gestational


age.


Fetuses


sterile


were


surgic


prepared


chronic


al procedure.


recordings


A midline


during


abdominal


incision


was


made


ewe,


through


which


fetal


head


was


extracted


and


instrumented


with


a bone


oscillator


electrodes


fixed


skull.


auditory


brain


stem


response


was


evoked


clicks


tone


bursts


500,


1000


and


2000


Hertz


delivered


through


bone


oscillator.


Pregnant


ewes


were


exposed


an intense


broadband


noise


decibels


carrying


sound


etuses


essure


level


at gestational


16 hours


ages


of either


while


days


(earlv


noise


-exnosed


around


S.J .t -J


days


(late


noise-exoosed


,









Auditory


brainstem


response


threshold


latency


increases


exposure


intensity


waves


were


entified


the late


means


immediately


noise-e


urements


entified


exposed


after


group.


three


fetal


four


sheep


were


noise


Latency-


vertex-positive


prolonged


.05)


after


noise.


Paired


t-tests


showed


that


res


ponse


thresholds


click


stimulus


were


temporarily


elevated


late


noise-exposed


group


0.01).


Although


there


was


no immediate


effect


on the


auditory


brainstem


response


early


noise-exposed


group,


when


ese


animal


were


tested


again


later


gestational


ages,


higher


thresholds


were


identified


noise-exposed


group


than


nonexposed


animals


one-way


analysis


variance,


.05).


Serial


celloidin


sections


cochleae


were


prepared


from


randomly-selected


noise-exposed


nonexposed


fetuses.


Cochl


ear


reconstructions


cytocochleograms


were


comply


eted.


sheep


cochlea


an unusual


shape,


with


long


basal


turn


a curved


modiolar


axis.


Light


microscopy


analy


organ


Corti


showed


unavoidable


preparation


artifact


because


unusual


coc


hlear


shape.


With


exception


preparation


damage,


cochleae


nonexposed


noise-exposed


groups


a similar


appearance.


nnnPnstratiT


Pciitl


n


cl-inMO/


fhht


m ln,


OYn rrrrr~

rr-n







fetal


auditory


brainstem response.


Light microscopy


show sensory


cell


differences


between noise-exposed


nonexposed animals.















CHAPTER


INTRODUCTION


Noise


everywhere


in contemporary


society,


permeating


environment


in which


people


work


relax


Noise


effi


known


ciency


to elevate


and,


stress


sufficiently


level


intense,


reduce


reduce


work


hearing


sensitivity.


relation


between


occupational


exposures


intense


sound


decreases


in hearing


acuity


was


first


reported


early


18th


century


Rama


zzini,


1713/1964


and,


since


then,


has been


widely


studied.


A 1991


U.S.


Public


Health


service


objectives


document


reported


that


noise


exposure


is respon


sible


hearing


losses


approximately


million


estimated


million


Americans


with


this


disorder.


1990,


was


reported


that


more


than


20 million


Americans


are


exposed


on a regular


basis


to hazardous


noise


levels


that


could


result


hearing


loss


NIH,


1990).


Significant


numbers


these


noise-exposed


Americans


are


women


Although


childbearing


hearing


loss


Moss


been


documented


Carver,


1992


in unprotected


individual


exposed


to hazardous


levels


noise


effects


Yrnns 1 re


l J


nn the


fetn 1Ses


nreanant


women


thepS











Noise-Induced


Hearing


Loss


Noise-induced


sensorineural


hearing


origin,


loss


affects


(NIHL


the hig


is described a

h frequencies,


occurs


insidiously,


worsens


with


continued


exposure.


severity


region


of cochlear


damage


largely


depends


on the


duration,


level,


spectral,


temporal


characteristics


noise


exposure.


Noise


"level"


refers


actual


sound


pressure


level


stimulus,


whereas,


noise


"exposure"


refers


combination


of noise


"level"


duration


stimulus


Lipscomb,


1988).


Assessment


of NIHL


Damage


Obtaining


measurements


of damage


to the


hearing


mechanism


following


hazardous-noise


exposure


is not


always


straightforward.


measurements


The


relation


of hearing


between


neither


cochlear


direct


nor


damage


one-to-one.


Pure-tone


behavioral


thresholds


are


uncertain


predictors


type


and


degree


inner


ear


pathology.


In animal


experimentation,


behavioral


measurements


have


added


disadvantage


time


needed


train


animals


correctly


obtaining


animal


respond


information


preparations


to signals.


about


following


Two


hearing


noise


popular


methods


mechanism


exposure


status


are


a aIC


a1A4 -rr -^ S^ r^ nr a -


1-I, 4-a .a


- --I..-


Lai^^-1^ ^^^-y-^


~rA


n


ci


w j- -h f i ui










Most


studies measure


the ABR


threshold,


but data


from


latency-intensity


are also used


functions or


to provide


latency-amplitude


information about cochle4


functions

ar damage.


Popelar


et al.


1987)


used auditory


evoked potential


recordings


shifts


from the


as well


inferior colliculus


as changes


found


in amplitude-intensity


threshold


functions.


Coats


and Martin


(1977


were among the


first


suggest,


in humans,


an effect on


the ABR with cochlear


hearing


loss.


They reported


that


high frequency


hearing


loss


affected


the ABR waveform by prolonging Wave


latency


more


than


Wave


V latency.


Additionally,


latency-


intensity


function


adults with cochlear


hearing


loss


steeper


usually


shorter than


for normal


hearing adults


(Galambos


and Hecox,


1978;


Yamada


et al.,


1979;


Picton


al.,


1981).


The main


features of


cochlear-damaged ABR are:


slope


latency-intensity that


increases


immediately


above


threshold;


normal


latency


for mild


and moderate


losses;


higher correlation between ABR


threshold and behaviorally measured


thresholds


as the


loss


increases.


Additional


studies


have dealt


with


relative


importance of


audiogram configuration and behavioral


thresholds


to pure


tones


(Jerger


and Mauldin,


1978;


Yamada


et al ..


1979*


Kpi th anr1 Cra7ill


19R71 -


The aamnint. nf











Cochlear


changes


Boettcher


et al.


(1987


summarized


possible


structural


changes


cochlea


following


exposure


to hazardous


noise.


Noise


can


damage


a variety


structures


in the


cochlea,


supporting


neurons.


cells


metabolism


including


cells,


lower


afferent


(Saunders


outer


blood

level


dendrites


et al.,


inner


vesse


hair


, secretary


of hazardous


may


1986;


noise


be damaged


Pujol


cells,


cells,


exposure


high


et al.,


hair


rates


1986).


level


exposure


increases


metabolism


may


be a lesser


factor


cochlear


mechanics


may


play


a greater


role


produ


cing


cochlear


damage.


Intense


noise


causes


tight


cell


junctions


to rupture,


allowing


perilymph


endolymph


mix,


thereby


destroying


electrical


chemical


balance


hair


cell


s and


causing


cell death


(Bohne


Rabbit,


1983


At still


than


decibels


higher


on the


levels


A-scale,


continuous


dBA)


noise


impulse


greater


noise,


cochlea


e.g.


can


be damaged


ripping


Reissner'


primarily


membrane


mechanical


or by


processes,


tearing


basilar


membrane


(Voldrick


Ulehova,


1982).


Borg


and


Engstrom


1989


found


structural


differences


coc


hlea


when


they


compared


short-term,


high-


level


exposure


30 minutes


long


-term,


low-level


A ft


1


*


1


r


I


r( 1


L irr r.


f


I t










stereocilia


loss of


a few outer


hair


cells


(OHC),


predominately


to 8


kilohertz


kHz)


region.


Conversely,


exposure


low-level,


long-term noise


showed no damage


to the


IHCs,


pronounced


loss/damage


the OHCs


as well


as a very


different


audiometric


configuration with damage


to 20 kHz


region.


They


speculated


degree of


that differing


contact between of


damage could be


Hensen's


related


stripe


stereocilia.


During exposure


increased contact between


to high noise


levels,


tectorial membrane


the

IHC


stereocilia


could


lead


to fatigue


and ciliary


fracture.


Henson's


stripe exerts direct


force on


stereocilia and


fatigue


stereocilia caused by mechanical


bending may


increase rapidly


as a


function of vibration amplitude.


This


supports


idea


a critical


level


where damage


IHCs can


occur.


findings of OHC


lesions


low-level


are compatible with


hypotheses


of metabolic


fatigue


low and moderate-sound


levels.


In an


attempt


to describe and quantify the


type of


damage occurring


the cochlea,


Rydmarker


et al


1989)


defined


10 different hair


cell


abnormalities:


The


absence of


cuticular plate and


presence


of phalangeal


scar.


This


been


most widely


reported morphological


damage


reported


from noise exposure


(Soudinn.


1976


: Encstrom and











with adjacent

appearance);


Giant


stereocilia but


Fused


stereocilia


were


bent


stereocilia,


(without


(floppy


still


fusion);


standing up;


Stereocilia


fusion with


the area


Dissolved


elongation;


on the


into


Shorter than average


basilar membrane where


the cuticular plate


length


located;


(melted);


Cuticular plate


protruded


from the plane of


reticular


lamina,


with


or without


stereocilia.


Pickles


et al.


(1987)


studied the effects


intense


sound


dB SPL at


hours


on stereocilia


linkage


guinea


pigs.


When


the stereocilia and


their


lateral


links were not disarrayed by sound,


links


remained


intact,


even


hair cells were close


to more


severely damaged hair cells.


spacing between


stereocilia


have been


was


lost.


increased,


Pickles et


links were more


(1987)


likely


hypothesized that


links were


initially


less vulnerable


than


lateral


links


or the


internal


core of


stereocilia.


However,


when


lateral


The


links


or the core were damaged,


pattern was different


than


links


the OHC.


fractured.


In OHC,


different


rows


stereocilia


their tip


links


seemed


equally vulnerable


to damage by


sound.


IHC,


tallest


stereocilia


were easily


detached


from the


next


row,


Tni I-h v-n vm'nl alao


4h- 4


1 _- 1


r r'0 nf r rl vn ri n I 1 n r a I r


1 --1--


Y


n v


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this could happen


stereocilia,


stimulus were


preferentially


coupled


tallest


stereocilia.


Once


links


joining them to


next


row were


broken by


an intense


stimulus,


stimulus could not be coupled mechanically


shorter


stereocilia,


they


their


links would be


isolated


from further


damage.


these


links


survived,


hair


cells could continue


transduce


signal.


Since


seems


that


stereocilia on


are moved by


viscous drag


still


be some mechan


surrounding corti

ical coupling of


lymph,


there would


stimulus directly


shorter


stereocilia


even if


the taller


stereocilia


were no


longer


functioning normally.


After


acoustic trauma


IHCs,


auditory nerve


fibers,


so presumably the


to which


they


are connected,


could continue


to respond


to a reduced


studied


level


effects of


sound.


intense


Canlon et al.


sound


(1987)


on stereocilia.


also


They


discovered


that,


after noise exposures,


stereocilia


became


less


stiff


and it


took


less


force


to move


stereocilia.


No structural


alteration


stereocilia


bundles was obvious,


Canlon


et al.


speculated


that


structural


differences


between


and OHC,


perhaps


stereocilia


core,


links or the cuticular region,


could


be responsible.


reaction


Another possible cause


in sti ffniPq rr l1, hs


for the differential


o 4n t r l T*7 ^T-k


I











Alterations


in the


tectorial


membrane


were


reported


Canlon


1988


after


guinea


pigs


were


exposed


tone


dB SPL


hours.


found


alterations


fiber


structure


membrane,

thickness


middle


discontinuit


stereocilia


tectorial

stiffness,


zone


Hensen


membrane,

swollen a


tectorial


s stripe,

localized

different de


reduced

reduction


ndrites


eath


IHCs


throughout


second,


third,


and


fourth


coc


hlear


turns,


swollen


supporting


cells


surrounding


IHCs


bodies


damage


swollen


such


an increased


cell bodies,


number


swollen


of Hensen


cuticular


plates,


and


Oss


sensitivity


with


maximal


eshold


shift


seen


between


kHz.


speculated


that


changes


tectorial


membrane


could


have


been


caused


dehydration,


depolymerization


fibers


as result


of mixing


inner


ear


fluids


or mechanical


stress


impact


tectorial


membrane


against


stereocilia,


causing


changes


fibers


Hensen'


stripe.


The


relation


between


ABR


histolocical


analv-


sis.


1987,


Borg


reported


that


immediately


after


exposing


rats


dB SPL


wide-band


noise


hours


per


day


month,


there


was


little


or no significant


loss


hair


cells


corresponding


to hearing


loss.


A 3-month


exposure


y -i iI e a: A .. Aa A 1 r A ar


F\3 faiT


/"* n tf^-


TW<\^rf y 4 f


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"Ml I l


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both behaviorally


and by the ABR.


After


15 months


noise


exposure,


hearing


loss


progressed,


loss of


OHCs


had progressed


even more and IHC


loss


stayed about


same.


Hamernik


et al.


1989


attributed different


behavioral


results


to nonhomogeneous


pathologies


fact


that


psychophysical


threshold reflects


totality


changes th

centrally,


Lat have

and not


taken p

simply


lace at

sensory


the p

cell


eriphery


oss.


as well

They


identified behavioral


results with 20


-40 dB hearing


loss


with no


sensory


cell


loss


and essentially normal


there


sholds


presence of


lesions.


Rydmarker


et al.


(1987)


wrote


that minor


damage


to hair cells can be observed


without changes


in hearing


sensitivity.


An impact


noise


hours did not cause


significant auditory threshold shift


as measured by


electrocochleography


from guinea pigs.


However,


there was


identifiable


hair cell


loss.


When


there


were


increased


threshold


shifts


to a


12-hour


impact


exposure,


there was an increase in minor


hair cell


damage,


only


a small


increase


in the number


of missing


hair


cells.


In another


study,


Price et al.


(1989)


stated


that


following noise exposure


and a recovery period,


lesions


could be


seen histologically


even when behaviorally measured


- -A. J.- -.-- - 1m


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a critical


level


damage


from impulse


noise exists,


then


in a condition near the critical


level


an average


ear,


less


susceptible ears would be


below this


individual


critical


level


and would


experience


losses.


Conversely,


other


individuals who are well


above


the critical


level


would


experience


serious


losses.


Price et


(1989


cautioned


that


hair cells may play


a major role


Corti,

place


in determining the


which determines


is resonant.


Therefore,


stiffness of


the organ


:equency at which a particular

assigning a particular place


on a cochleogram to a


not have


tonal


same meaning


frequency


assigning


in a damaged


frequency


ear may


in an


undamaged ear.


Borg


and Engstrom


1989


questioned


the underlying


assumptions


using


audiometric values


to interpret


cochlear


that


site


hearing


damage.


loss grows at


Traditionally,


frequency


was


believed


in question,


rather


than


damage


being


shifted


frequency.


Findings


that


show


different


exposure


frequency


support


of hearing


the argument


loss


for different


against


levels of


traditional


view


of a one-to-one cochlear place/frequency


relation.


Thus,


use of


averages


over


the entire


frequency


range


several


selected


frequencies may


be preferable


than


- --- -- ---


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L










decrease


in stiffness with


increasing


exposure duration.


contrast,


ABR thresholds


showed dependent change


sensitivity with increasing


exposure duration.


Secondly,


study,


stereocilia


stiffness


returned


to pre-


exposure


thresholds


after


a recovery period,


while ABR


thresholds were


that


still


decreased by


an oversimplification


stereocilia are


responsible


She concluded


to assume that


for decreases


only the


in auditory


sensitivity.


Even


though


IHCs


have most


the afferent


connections,


the OHCs contribute


to the


improved auditory


sensitivity.


Lonsbury


et al.


(1987)


found


that


their


level


of OHC


loss


in all


animals


correlated poorly with more


extensive


frequency pattern


of behavioral


threshold shifts,


also


suggesting that extensive


threshold shifts cannot be


accounted


stereocilia alone.


the other


hand,


Davis et al.


1989)


found a


systematic


relation between


the degree of permanent


threshold


shift,


abnormal


populations and changes


quality


tuning.


They reported detectable changes


tuning curve


high-frequency


slope


low-


frequency


slope


when


permanent


threshold shift


exceeds


and concluded


that


changes


in tuning


are


related


primarily to


systematic


loss of


OHCs.


A lack of


correlation between hair cn1 1


1 om


ann











will


shift


some


tuning


curves


Engstrom


Borg,


1983).


firing


rate


nerve


ers


from


adjacent


normal


IHCs


could


increase


sufficiently


to compensate


shifted


tuning


curves


leave


ABR


behavioral


thresholds


larg


unaffect


damage


affects


greater


number


IHCs


corresponding


tuning


curves


in a particular


region,


the auditory


thresholds


would


shifted.


this


case


, there


would


intact


nerve


fibers


immediate


vicinity


to compensate


those


with


shifted


thresholds.


Fetal


Hearing


Development


Embryologi


cally,


ear


matures


from


an ectodermal


thickening,


call


ed the


auditory


placode.


placode


develops


into


a vesicular


shaped


pit,


termed


otocyst.


In humans,


at about


to 5


weeks


gestational


GA),


the


otocyst


divides


into


lobes,


labyrinth


coc


hlea.


At 6


months,


both


organ


Corti


tunnel


Corti


are


present


in all


turns


cochlea


and


about


24th


week,


cochlea


peripheral


sensory


organs


have


reached


their


normal


development


(Gagnon,


1QRQ \


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*r fl//iior ai


1 QQI \


htrmnTi-


-I" r~


I


d










by parallel


chronology


from other


species


that


human


organ


of Corti


functional


to 20 weeks.


this


time,


auditory


neural


pathways


are


functional,


although


the myelination


process


that


starts during the


20th week of


fetal


life


is not completed at birth.


appears


that


normal


growth and maturation of


brain depends on an


intact


auditory


system.


This was


demonstrated by the


impairment


glucose utilization


auditory


as well


as nonauditory portions of


the brain after


cochlear


ablation


fetal


sheep


(Abrams et al.,


1987).


Harris


et al.


1990)


found that


the gerbil,


ces


station


growth


the cochlea


occurs


before acoustic


stimulation


first evokes cochlear


responses and


that


cessation


basilar membrane growth


immediately precedes


the onset


function.


Walsh and McGee


1990)


suggested


three


stages


development


in cats.


During the


first


stage,


thresholds


are


very


high and well


outside of


the range


naturally


occurring


acoustic events.


Response


sensitivity


does


significantly


improve during this


period,


response


frequency


range


is restricted


to low-


and mid-frequencies.


They


believe


that


second


stage


is characterized by


rapid


improvements


in threshold and acquisition of


adult-like


organization.


Changes during thi


staqe would


include


___











formation


membrane,


third


of hydraulic


organ


stage,


fluid


of Corti i


remaining


spaces


adult-like


.nnervation


components


patterns.


mature


tectorial


During


and


myelination


completed.


Rubel


1984


wrote


that


single


event


triggers


onset


coc


function,


hlear


there


function"


are


many


(pg.


Before


simultaneous


onset


synchronous


events


contributing


maturation


of mechanical


and


neural


properties.


These


events


include


a thinning


basilar


membrane,


formation


inner


spiral


sulcus,


maturation


pillar


tectorial


cells,


membrane


eing


, development


inferior


tissue


margin


spaces


the


the


organ


of Corti,


differentiation


hair


cells,


establi


shment


of mature


stereocilia


structure,


and


the


maturation


synapses.


This


synchrony


development


was


observed


with


mice


1978


(Rubel).


majority


cell


types


underwent


terminal


cell


oses


on day


14 GA.


These


cell


types


included


spiral


ganglion


cells,


IHCs,


OHCs,


inner


pillar


cells


outer


pillar


cells,


Deiter


s cells,


Hensen


s cells,


Claudius


cells,


inner


supporting


cells,


and


ernal


sulcus


cells.


Rubel


suggested


either


a common


origin


or some


active


process


regulating


the synchronization


of proliferation.


I


na. -A -A -


1L-.%- .. .. .. A


SL L m k











development.


Additionally,


a radial


development


from


modiolus


to stria


vascularis occurs.


Longitudinally,


humans,


differentiation


spreads


occurs


in both directions,


first

with


the mid-basal


the apex maturing


region

last.


In radial


development,


synapses


form early


on IHCs


change


little


thereafter.


The OHCs


mature


later


than


IHCs


and are


initially


surrounded by


afferent


terminals


which are gradually


replaced by numerous


large calyciform efferent


terminals


efferents.


form,


Then,


which are


typical


the mature cochlea.


Consequently,


there


seems


to be


some


sort


"autoregulation,


" that


allows


simultaneous


growth and


destruction


of cell


types


that


leads


to a cochlea


that


electrically,


chemically,


and mechanically


capable of


rudimentary


function.


Rubel


and Ryals


(1983


found in chicks


that during the


late


stages of maturation,


position of


hair


cell


damage


on the


basilar membrane


shifts apically with an


exposure


an intense


caused


1500


pure


region of


hair


tone.


cell


The exposure of


loss


older


to be shifted


animals


toward


apex.


These


results


suggest


that


the region


the basilar


membrane


that


maximally


activated by


a relatively


frequency tone


a basal


location


initially


then,


with


incrrFeasi nr


c III 1l *I ii I a1 c fnn l


.hi fft


t nwa rd


;InPa


ar1Pv


I I 1l-


1| r| i











The development


active


process may


the main cause


frequency/place coding


shift.


Norton


et al.


1991)


reported an


orderly progression


the appearance of


otoacoustic


emissions during


gerbil


development.


They


concluded


that


"initially


cochlear


mechanics


are


passive and


that


active


elements


associated


with normal


function mature


first


the basal


turn and


last


near the apex"


(pg.


73) .


Walsh and McGee


(1987,


1990)


argued


that additional


system has


begun


support


to function is


for OHC maturation after the

provided by the auditory


nerve


tuning curves


recorded


from neonatal


kittens.


These


recordings


exhibit high


thresholds,


saturation levels


excess


125 dB SPL,


small


dynamic


ranges and


low maximum


discharge


rates.


similar to


These characteristics are


input-output


curves


strikingly


noise-exposed ears


adult


animals.


Studying


guinea


pigs,


Pujol


et al.


1991)


found


that


appearance and development of


the OHC motilities


vitro


follows


a base-to-apex gradient.


Prior to onset


motility,


OHCs acquire an adult-like distribution


microfilaments

of motility co


and intermediate


incides


filaments.


at gross morphological


Also,

level


the onset

with an


increase


in the


length


ml......


the cell


- In a -


k T q I r, f1.J | E ,I I


its

th->


h r. T7 Tr r-


regular

* *ho ninat


r*r1 n1r^/a


*C 1A











onset


of motility,


corresponds


to a regular


alignment of


one


layer


of cistern along the


lateral


plasma membrane.


intrauterine


sound


environment


Typically,


most


noise exposures


occur


in an air


medium.


fetus


an exception


that


sound


energy


must


pass


from the air medium to


fluid medium of


amnion.


changes media,


sound energy


reduced


because of

interface.


impedance difference at


The acoustic


impedance of water


the air-tissue


is much higher


than air.


a given pressure disturbance,


particle


velocity


Therefore,


is much


equal


less,


pressures


a factor


in air


approximately


fluid differ


3600.


sound


energy


approximately


36 dB


(Gerhardt,


1990).


Thus,


one


would assume


that


sound


pressure


required


to produce a


physiologic r

36 dB greater


response

than t


from the


fetus would be approximately


he sound pressure


in air necessary to


produce


1992).


same


Factors


reaches


inner


response


that determine


ear


from the newborn


how much


fetus


(Gerhardt


ex utero


include


et al.,


sound


sound


pressure attenuation


through maternal


tissue and


fluid and


transformation


these pressures


into basilar membrane


displacement.


Diaestive and resoiratorv


sounds


dominate


the internal











environment


was monitored with


a hydrophone.


Sounds


mastication,


detected above

experimenters


swallowing,


the

three


noise

feet


physical


floor an

from the


movement


d conversations


ewe were


were


easily


between


recognizable.


Speech was muffled


intelligibility was poor.


However,


pitch,


intonation and rhythm were clear,


suggesting


that


maternal


voice


forms a


prominent


part


a rich


intrauterine


sound


environment.


The observations above


as well


as hydrophone


measurements


suggest


that


intrauterine


sound


environment


functions


as a low-pass


filter.


Measuring the


sound


environment


pregnant


sheep with a hydrophone,


Gerhardt


(1990)


Gerhardt,


Abrams,


and Oliver


1990)


reported


that


sound


For


environment


frequencies


is dominated by


below


frequencies


reduction


below 500


in sound


pressure


through maternal


tissues and


fluids was


less


than 5


Above


attenuation


increased at a rate of


octave


attenuation was


up to approximately


to 25 dB.


4000


where


Therefore,


sound


the average


transmission


fetal


head


through


intrauterine


tissue


is more


efficient


low frequency


sounds


than


higher


frequency


sounds.


The amount


of basilar membrane displacement


with


fetal


- -- -I~ -- -- I - - -


SS


- -


* 1 J


* -


_I


1


; I











neural


mechanisms.


Basilar membrane displacement,


caused by


hydraulic motion


the cochlear


fluids,


must


occur


IHCs


and OHCs


to be


stimulated.


the normal


adult


system,


stapedial

fluids in


movement


motion.


in and


the oval


fetal middle ear


window sets


external


the

ear


canal


are


filled with amniotic


fluid,


which decreases


mechanical


advantage


the middle ear.


In addition,


sound


pressures may


windows.

lack of


be present


The lack of

a middle ear


with


same phase at


a phase difference,


amplifier may


in addition


substantially


decrease


basilar membrane displacement,


therefore cause


decrease


hearing


sensitivity.


the other


transmitted


hand,


from the outer


sound may


ear through


be efficiently


the middle ear to


inner


ear.


Querleu


et al.


1989)


wrote


that


The middle ear
audition. Bec


is not


necessary


cause the outer


fetal


and middle ears


are


filled with amniotic


fluid and because


liquids,


tissues


and bones


have close conducting


properties, th
uterine cavity


e acoustic energy


can reach


with negligible energy


inside


the cochlear


loss


in utero.


the
receptors
Thus,


there


is no need for


an amplifying


system.


(pg.


410)


Because all


cavities


are


filled with


fluid,


there


less


impedance mismatch between


the outer


ear


inner


ear,


less


middle


need


ea r


for the


However.


impedance matching


nhaftr off


function of


snn nd


It m


Inr^Rpsnr-


L_ i i "'


1


1 1 l "


Cflr-










stapedial movement


vibration


will


stapes


occur.


Without a


footplate with respect


skull,


basilar membrane displacement


will


occur


or will


greatly reduced.


Without


knowing the effect


intrauterine environment


fetal


on stapedial


basilar membrane displacement


movement,


caused by


amount


a known


sound


pressure


fetal


head cannot


be determined.


Assessment


of Fetal Auditory


Function


Assessment


fetal


auditory


function


can be


accomplished by


histological


and/or


electrophysiological


methods.


Recent


studies


using


electrophysiological methods


have


allowed


utero measurements of


the ABR


in pregnant


ewes.


Sheep


have


been


used in


these


types


studies


only


because


pregnant


sheep


have


similar dimensions


pregnant


women,


but also because of


similarity


in adult


sheep and


human minimum audible


field measurements


(Wollack,


1963;


Heffner


and Heffner,


1985).


Woods


et al.


(1983)


obtained


fetal


sheep ABRs using


a modified hearing


aid


amplifier to


transduce


stimulus.


In later


studies,


Woods


and Plessinger


(1985


and Woods


et al.


(1987


reported


observation and lat


enc


five


vertex positive waves


fetuses


of GAs


days and


lambs


of GAs


Min rAQ n ro+ n n hl a r n nnc c rn m 1 dr ho


1 ricnt; i; P F^


I .LI.











consistent


responses


no earlier


than


118 days.


their


study,


Waves


were observable


days when


the ABR was


first


elicited and Waves


IV and


V were


observed


several


days


later.


The modified hearing


transducer may


have


provided


best


stimulus


obtaining


ABR.


Wolfson


1990)


obtained bone-conducted ABRs


from


sheep


fetuses


utero


as early


106 days GA.


this preparation,


fetuses were delivered,


and maintained on a


life-support


system while


the ABR was


recorded.


Wolfson


1990)


reported


age-related


changes


in the ABR,


suggestive of


substantial


brain-stem maturation between


days


gestation.


Gerhardt


et al.


(1992)


recorded in


utero cochlear


microphonics


(CM)


from fetal


sheep at


109 days.


Presumably,


the CM precedes


first appearance of


the auditory


brainstem response


in sheep


it does


in other precocious


animals.

days GA


The CM recordings


were


from animals younger than


not attempted for this


study.


Fetal


noise-induced hearing


loss


Evidence concerning the


existence of


fetal


noise-


induced hearing


loss


is equivocal.


Dunn


et al.


1981)


exposed


pregnant


sheep


dB SPL broadband


noise


hours a dav.


davs a


week.


.5 a


months.


After


delivery.


A-










a control


group.


Although morphological


changes


were


found


to be


twice


frequent


in the


noise-exposed


group,


preparation


artifacts


could


be excluded


a cause


observed


cochlear


damage.


In contrast


Dunn


study,


1991


fetal


sheep


study


(Pierson


et al.,


1991)


measured


the ABR in


utero


before and after


identified


16-hour,


significant changes


broad-band noise exposure.


in ABR latencies


They


elicited by


a broadband click


stimulus.


Whenever there was a


significant difference between


pre-


postexposure


measurements,


postexposure measurements


had a


longer


latency.


Cook et


1981)


exposed a


group of


pregnant


guinea


pigs


last


trimester


of pregnancy to


dBA of


tape-


recorded loom noise


and after


birth,


compared ABR latencies


to a


latency


nonexposed


group.


differences


They


that


they


reported consistent


attributed


Wave


"direct


overstimulation


the developing


auditory


system"


101)


or to


"abnormal


pathway development


following noise exposure


during


critical maturation


periods"


(pg.


101).


Additional


support


possibility


of hearing


changes


subsequent


to noise


exposure was


provided by


Lalande


et al.


1986).


They


found an


increased risk


of hearing


loss


in children whose mothers were occunati nall 1v


exnnsed


I. L










frequency


4000


Hertz


(Hz)


when


the exposure


involved a


strong component


low-frequency noise.


Some


researchers


have expressed concern about


antepartum fetal


stimulation with an


electronic


artificial


larynx


(EAL


(Gerhardt,


1989;


Gerhardt


et al.,


1988).


Noise


levels


from the


EAL in


intrauterine environment averaged


between


dB depending


on the distance


from the


hydrophone.


These


levels


are well


above occupational


levels


considered


potentially


hazardous


to unprotected hearing,


depending


on duration


(Occupational


Safety


and Health


Administration,



The critical pe


1981).


!riod


Cook et


(1981


suggested


that a critical


period of


auditory


development appears


to coincide with


or closely


follows


finalization


auditory maturation processes.


Some


researchers


have


found increased susceptibility


NIHL


at particular periods of


auditory


development.


These


investigations


involve


study


of a variety


animal


species with


undeveloped hearing mechanisms


at birth.


Consequently,

However, there


generalizing


:e are


results


similarities


to humans


is difficult.


in NIHL susceptibility


among


these animal


species.


Bock and Saunders


1977


identified.


a-A.


hamsters.


&










threshold


after


noise exposure occurred during


a period


CM threshold


improvement


in the nonexposed


control


animals.


Price


1972,


1976),


using cats,


also


found


that


young


animals were more


susceptible


than adults


to changes


in the


CM after


dB SPL,


tone


50 minutes.


Saunders


Hirsh


1976


determined a


similar


critical


period

Lenoir


an increase


et al.


action


(1979)


potential


in CM threshold


found

(AP)


in mice.


the maximum effect


threshold measurement


the rat,


noise on

occurred at


22 days.


time course of


increased


susceptibility


appears


to vary by


species,


but appears


to follow a


pattern


of maximum susceptibility


some


time after


onset


auditory


function,


instead


of concurrently with


the onset


function.


Saunders


and Bock


1978)


could not


speculate


the cause of


time course of


the critical


period since at


time of


responses


increased NIHL,


appear


the cochleae and physiological


developed.


In a histological


study,


Falk et


(1974


identified more


IHC and OHC


young


guinea


pigs


than


adult


guinea


pigs


month after noise exposure.


Within


young


animals,


there was


a trend


towards


greater


amount


cellular


damage


in the group exposed


on the


second day than


the group exposed


the eighth day.


It annears t


hat.


least


n soecies with


immature


i


..











susceptibility with


species


that develop


hearing


utero


well


understood.


The objective of


this


study


is to contribute


to the


understanding


in utero


hearing development


investigating the


utero development


of hearing


fetal


sheep,


determining the effect


of a noise exposure during


what may be a critical


period of


development,


observing


hair


cell


status


in both


the normal


and noise-exposed


sheep


fetus.














CHAPTER


OBJECTIVES


AND METHODS


The overall


aim of


this project was


to evaluate


hazards of


over-exposure


noise


on the


in utero


development


the auditory


tern of


fetal


sheep.


Changes


produced by noise exposure at


two different


GAs were


evaluated


through


the use of


electrophysiologic


histologic methods.


Auditory


function was assessed


from ABR


recordings


to click and


tone burst


stimuli.


Cochlear


changes were


assessed by


a histologic method


reconstructing cytocochleograms


from serial


celloidin


sections.


To meet


the above aim,


two experiments,


one


longitudinal


one cross-sectional,


were completed.


purpose of


first


experiment was


assess


effect


of noise-exposure at a


particular GA on auditory


system development.


structural

exposed fe


structural


this


development


tuses were compared


development


experiment,


the auditory


functional


system of


functional


auditory


and


noise-

and


system in non-


exposed,


age-matched fetuses


from


days GA.


The


ABRs


various


groups.


were


In addition,


recorded and compared between


animals were


sacrificed and











purpose of


second


experiment


was


to determine


delivery


an intense


noise


to an


early GA


fetus versus


a later GA


fetus creates differences


in ABR responses and


cochlear


structure.


this experiment,


fetal ABRs were


recorded and compared before and after noise exposure at


two


different


GAs.


Five days


after noise exposure,


the cochleae


from representatives of


these


two groups of


fetuses were


removed,


prepared and


sensory


cell


were described.


Subjects


Thirty-four,


subjects


time-mated


pregnant ewes provided


these two experiments.


The ewes were


fetuses


housed


individual


stalls


' by 8


to 5 days


before


surgery to allow them to acclimate


the environment.


Following


surgery


each


treatment condition,


ewes were


returned


these


stalls.


the conclusion


experiment,


ewes were euthanized with a


concentrated


barbiturate


solution administered


through


previously


implanted intravenous catheters.


Temporal bones


from


selected subjects were


removed rapidly


and prepared


histologic


analy


S1S.


Gestational


ages


time of


noise


exposure were


days


(+/-


days).


Subjects


numbered


005,


008,


010,


01I 01l_ an0 n


nrS fx0n71 nl nvnri Tnnn rnnmnrri 0c


I h I I I











exposure


noise


as well


after


recovery


period.


cochleae


subjects


were


harvested at


days


"early-exposed"


group


consisted


ewes


surgically


prepared


surviving


ewes


were


functionally


expos


tested


noise


ages


and also


111,


preexposure


functionally


tested at


stexposure


116,


130,


131,


dGA.


For


cross-


sectional


study,


animal


were


sac


rificed


dGA,


cochleae


removed


prepared


histology.


remaining


animals


, six


subjects


were


evaluated


through


days


five


ese


animals


were


evaluated


through


days


these


animals


provided


cochleae


ology.


The


"nonexposed


group"


consisted


of nine


animals


surgically


prepared


days


ABR


testing


was


comply


eted


on surviving


animals


according


same


schedule


evaluated


as the


early-exposed


through


dGA


group.


five


animals


animals


were


completed


protocol


through


dGA.


coc


hleae


from


animals


sacrificed


days


were


prepared


stology.


Animals


"surgery


only"


group


were


instrument


were


test


ed and


coc


hleae


were


removed


prepared


histology


days


"histol


ogy


only"


qroup


subi


ects


were


sac


rificed


Y I


I .


Y 1 .











Procedures


Surqerv


To record ABR


from


the in


utero sheep


fetus,


sterile


surgery was


required


to apply the


necessary


chronic


instrumentation.


The ewes were brought


into


surgery


room and anesthetized with halothane.


equipment


instruments


had been gas


sterilized.


fetal head was


exteriorized


through a cesarean


incision.


The


fetal


skull


was


exposed by retracting overlying tissue,


electrodes were secured midline


nostral


to the


screw-

frontal


bones,


in the vertex and


in both mastoids on


or near the


head


styloid


process.


To provide


insulation and


additional


stability,


the electrodes were covered with


methyl


methacrylate.


bone oscillator was


secured


central


fetal


skull


on the parietal


occipital


bones


caudal


as possible.


Two rows


three


screws


each were


fixed in


skull


the oscillator was


secured


between

The


them with


thread.


incision was closed over the electrodes


and around


bone


oscillator.


Also,


a catheter was


placed in


femoral


artery


the ewe.


fetus was


returned


to the


uterus and

Al wirs<


WPrA


uterus

na cct qH


and abdomen


l1nh4mr th matrn 1


ewe were closed.

aci n nnu+










maternal


flank.


To protect


pouch,


ewes


wore an


elastic


piece of


material


around


their bodies


over


pouch.


The ABR


Equipment


Electrical


signals


from the


fetus


in response


acoustic


stimuli


were


recorded by the Tracor Northern


(Model


TN3000)


computer


averaging


system.


Signal


were


differentially


recorded,


amplified


100,000


fold


filtered


(0.1-3.0


kHz),


averaged and stored


on disk


later


analysis.


Six bone oscillators


(Radioear


B70A


, closely matched


output and


labeled A,


23179,


were


used


to provide


the acoustic


stimulus


to the


fetal


heads.


Each


oscillator was


sealed with acrylic


around the


seam and wire


connection


to preclude


fluid damage.


The outputs


bone oscillators were calibrated with an accelerometer


fixed


directly to


the vibrating


surface.


Accelerometer


output


was


directed


to a


spectrum analyzer


(Bruel


and Kjaer,


B&K,


model


2123).


amplitude


osc


and spectral


illators was compared


characteristics


each bone oscillator


the

for


bone

each


four


stimuli


(broadband


click,


kHz,


2kHz, and .5


m


__ m w.










labeled


shown


on a


one-twelfth


octave


band


scale


appear


in Figure


2-1.


Stimulus


levels


fetus can


only


estimated because of


the direct


placement of


the oscillator


on the


skull


as well


presence of


a fluid-filled


environment.


Stimulus


level


(dB nHL


was


referenced


young


normal


human


=5)


behavioral


thresholds with a


bone


oscillator placed on


the mastoid.


Recording the ABR


With


the exception


of one animal


that


was


tested


hours after


surgery,


testing


from fetuses


occurred at


least


after


surgery.


On all


days


ABR


testing,


ewe was


room.


placed in a


fetal


cart and positioned in a


electrodes were connected


sound-treated


to the Tracor


Northern ABR averaging unit.


two electrode


leads


positioned


the mastoids were


linked


together


connected


to the


inverting


input of


the amplifier.


vertex electrode was connected


the non-inverting


lead


amplifier


snout


electrode was connected


ground


input


the amplifier.


The ABR was


sampled


2000


trials


average over


18 millisecond


(ms)


window for


tone


bursts


and a


10 ms window


clicks.


Broadband


clicks with a


.1 ms duration


tone


bursts


kHz with a


two cycle


rise/fall


time and one cycle duration


















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tone


burst


with


cycle


rise/fall


time,


duration


was


presented.


Responses


were


rec


orded


starting


80 dB


on the


Tracor


unit


decr


ease


d in


20 dB steps


until


response


was


longer


identified.


Then


level


was


increase


ed by


and


dB steps


until


an ABR


threshold


was


reached.


Replications


respon


ses


were


completed


to support


absolute


latency


and



The


threshold


Noise


identification.


Exposure


Equipment


noise


exposure


was


presented


in an


sound-treated


booth


(Industrial


Acoustics


Company,


model


GDC-1L).


A 120


dB SPL,


broad-band


noise


was


delivered


sides


ewe


through


four


loud


speakers.


Speakers


were


placed


near


both


flanks


as well


as above


and


behind


the


back


with


ewe.


aB &


AB &


K one/half


K sound


inch


level


microphone


meter


was


(model


used


2209


to check


noise


levels


around


ewe


before


exposure


begins.


the maternal


flank,


noise


levels


within


dB of


dB SPL


were


accepted.










dB SPL broadband noise


Maternal


sound-field


hearing was protected by


hours.


foam hearing protectors


placed


the external


ear canal


secured with


tape


around


the pinna.


Histoloqical Methods


Obtaining the cochleae


Cochleae


A medial


from fetuses were


obtained at


incision was made on


the designated


head rostrally


from


above


eyes


the base of


neck.


Cochleae were


removed by


breaking through


foreman magnum with rongeurs


and carefully


bone.


cutting


away the bone


Formalin was perfused


windows


the cochleae were


through


stored


surrounding the


the oval


formalin


temporal


and round


until


decalcification process.



Decalcification and dehydration


Cochleae were decalcified by


immersion


in a


aqueous


solution


tetrasodium Ethylenediaminetetra-acid


(EDTA).


The cochleae were


placed


in a


series


alcohols


increasing concentrations


each and


(50%,


then placed


70%,


100%


80%,


ether


95%,


100%


alcohol


another


day.










Embeddinq


sectioninq


In a method similar


to Schuknecht's


1953),


cochleae were


12%)


placed


increasing concentrations


of celloidin


week each.


(2%,


After


bones


had been


12% celloidin


week,


top of


the celloidin was


hardened with chloroform,


and


excess


celloidin was


trimmed


to create


rectangular


blocks.


blocks were mounted


on cutting blocks


so that


vertical


horizontal


sections could be cut with a sliding microtome


knife


American Optical


Company,


model


860).


Sections were


thicknesses


20 microns,


placed on numbered paper,


every


fifth


section removed


slide preparation.


Sections were consecutively numbered beginning


apex


and proceeding toward


most aspect


the base or beginning at


the cochlea and


lateral


proceeding medially.


Stamina


and mounting


The


sections were stained with hematoxylin and eosin


a method


similar to


that described by Schuknecht


(1953,


1974).


sections were


rinsed


50% alcohol


and


then


distilled water


placed


in Harris


Hematoxylin


minutes.


They were


rinsed in


sequence


in distilled water,


acid alcohol


amTmnrn n


until


t7 tr 1 irn* 1


pink in

1,1a10


color,


n r'nl IrT


distilled water,


"' Ir-


can4 i n nn LTxor


then

than










placed


in a


one-to-one alcohol/chloroform rinse.


Finally


sections were moved

rinse and mounted o


through a


n glas


one-to-one


slides.


terpineol/xylene


A mounting medium was


used


to place


section and


the cover


slip was pressed


into


place.


Organ of


Corti


description


Measurements


tangential


cuts


through


the organ


Corti

Each


were made and placed along a

cochlear turn was measured as


n axis on graph


paper.


the distance between


heads


the pillar cells


along


adjacent


turns


and were


plotted


on graph paper,


producing a


spiralgram.


The organ


Corti


was


represented as a


series


of observations


of OHCs


IHCs.


Each


series consisted


of observations made


from


every


fifth


section indicated above.


Each normal


hair


cell


was


recorded as a


large open dot


relative


location


within


the box.


Abnormal


appearing


hair


cells were


represented with


filled dots.


Absent


hair


cells were


represented by


x's.


When


the observations


had been made,


the dots and


placed


proper


location,


reconstruction


the cochlea


appeared.


Areas


of missing


hair


cells were


plotted


in a


histogram,


termed a


cytocochleogram.











Design


Animals


in the


nonexposed,


early-


and


late-exposed


groups


were


used


both


ABR


assessment


histol


ogy


surgery


only


histology


only


animals


were


used


structural


evaluation


coc


hlea


assoc


iated


sensory


components.


Experiment


purpose


this


experiment


was


assess


the


effect


noise-exposure


at a particular


on cochlear


development.


Two


experimental


questions


were


addressed:


Does


noise


exposure


delivered


day


GA fetus


have


an effect


Does


on the


stologic


continuing


development


integrity


cochleae


ABR?


harvested


days


GA from


nonexposed


early-exposed


groups


differ


qualitatively


answer


question


one,


only


nonexposed


early


noise-exposed


groups


were


considered.


The


ABR


was


recorded


intervals


designated


above.


Mean


thresholds


latencies


were


determined


each


stimulus


type


level.


ABRs


recorded


from


nonexposed


group


were


compared


to GA-matched,


pre-


postexposure


ABRs


from


early


noise-exposed


group.


rn-AA .. k a n- .-a 4,nnnf i -a- ,A -


nnn


,,,,,f


,,,,~C


E1,1 ,-,


Ck


-If--











purpose of


surgery


only


and histology


only


groups


was


assess


the effect of ABR stimulation


and surgery


coc


eae


by comparing them to


nonexposed group.


Table


provides


synopsis


events


that


occurred


answer the questions


in Experiment


One.


Experiment


Two


purpose of


this


experiment was


to determine whether


intense


noise delivered at an


earlier GA creates different


amounts


of change


in the auditory


system than a noise


exposure delivered at a later GA.


two experimental


questions addressed were:


Does


intense noise create


different changes


in the ABR recorded from in


utero


fetuses


exposed at


113 days GA


versus


fetu


ses


exposed at


130 days


Do the cochleae harvested


5 days


after noise


exposure


have a similar


appearance when


exposure occurs


an early versus


late GA?


The ABR data


from the early


and late


noise-exposed


groups were


used


to address


first question.


Mean ABR


thresholds


latencies


were compared


from late noise-exposed


early noise-exposed


group.


fetuses


Differences


in the


preexposure,


postexposure


48-hour recovery


ABRs


were


assessed.


mr a n nn r y


crrioC+ i nfl


-T.tr


rrnnhl ann


Fr nm arr17


-4


S1 I-A,












Table


Experiment


Timeline.











group


harvested at


days GA,


were described.


noise-exposed cochleae were


harvested


fifth day


after


the cessation


noise exposure.


Table


provides


a synopsis of


event


completed


answer


the ABR and histologic questions


of Experiment


Two.


Data Analysis


Identification of peaks and ABR thresholds were


determined by two


recording techniques.


independent


observers experienced in ABR


Latency measurements


vertex-


positive


peaks


clicks,


kHz were


recorded with


one


the observers


blinded


to treatment condition.


Differences


in latency


scoring were


resolved by


averaging


latency values,


there was


less


than a


difference.


Differences


greater


than


0.1 ms were


resolved


reexamining the waveform.


thresholds


clicks,


kHz,


.5 kHz were defined as


lowest


level


which a


positive ABR waveform was


Analyses


the ABR thresholds


identified.


latencies were


completed


using


one-way


analysis


of variance


for t-tests.


Differences


in the mean absolute


latency values


clicks


and


kHz,


accounting


stimulus


type,


level,


age at


exposure,


exposure condition,


were


simultaneously


rnmn2Tr0A -


*1 5 f o r nnr 'oc


SNT


*Io mno-n AXnQT


*^raChlk Al


fnr rFi4 Ft-V













Table


2-2.


Experiment


Two


Timeline











level


were made


for GA,


age at


exposure,


exposure


condition were compared.















CHAPTER


RESULTS


AND


DISCUSSION


Subiects


Thirty-four


animals


were


utilized


this


study,


24 completed


protocol.


Twenty-eight


animals


were


instrumented


ABR


measurements


and


grouped


follows:


nine


in the


nonexposed


group;


thirteen


in the


early


noise-exposed


group;


late


noise-


expos


group.


animals


were


used


only


histology,


were


instrumented


ABR.


preparations


that


failed


to complete


protocol,


there


were


three


instances


of bone


osc


illator


failure


in an otherwise


healthy


animal,


one


ewe


death


after


surgery,


fetal


deaths


after


surgery,


five


abortions


or early


deliveries.


cochlea


from


each


three


subjects


was


damaged


during


proce


ssing.


These


coc


hleae


were


excluded


from


histologic


analy


S'S


and


the


contralateral


cochleae,


also


available


from


ese


animals,


were


chosen


preparation.










Nonexposed Subiects


Normal ABR Development


animals


dGA,


this


group were prepared


generated ABR measurements


surgically

after


surgery,


Chapter


followed a


and were


testing


schedule


sacrificed


indicated


136 dGA.


The ABR


morphologies,


thresholds,


and latencies


showed rapid


development


from


136 dGA.


Figure


shows


click-evoked ABR


changes


that


occurred


over


time


typical


nonexposed


subject.


dGA,


the ABR was


present


in all


ABR-instrumented


subjects


(nine


from


nonexposed


group plus


from the early noise-


exposed group),


who


undergone


surgery


110 dGA.


The morphology

indicative of


the waveform,


a positive response at


although repeatable


41 dB nHL


(the


output


limit of


the bone vibrator without distortion),


did not


typically


allow for the


identification


peaks.


subjects


tested at


dGA,


only


one


produced any


repeatable


peaks.


A positive


response


dGA


was characterized by


the waveform at


around


a positive deflection


ms or a negative drop that


emerged at approximately


By day 116 dGA,


7-8 ms.


ABR waveform morDholoov









1 uV


111 dGA


113 dGA


114 dGA


116 dGA




123 dGA




130 dGA




136 dGA










nine


subjects


the nonexposed


group produced reliable


ABR waveforms with


four vertex positive peaks.


By this


time


the early noise-exposed


group of


animals


had been


exposed.


The morphology


the ABR continued


improve


dGA,


when


the click-evoked ABR in


fetal


sheep was characterized by


"four"


peaks


waveform.


dB nHL,


Wave


had a mean


latency


1.75


Wave


2.61 ms;


Wave


III,


3.85 ms;


and Wave


4.59


ms.


presence of


"four"


peaks were


in agreement


with


observations of Wolf son et al.


1990),


from


exteriorized


premature


lambs


but contradicted


"seven"


peaks


identified in


lambs


Ashwal


et al.


(1984)


Plessinger


"five"


(1985)


peaks


and Woods


fetuses


et al.


by Woods and


1987).


morphologies


fetal ABR waveform recorded


current


study


recorded in


differences


fetal


previous


in the number


lamb ABR waveforms


similar.


of waveform peaks


explained by peak


"labeling,


" with


their peaks


I-IV


corresponding to


peaks


I-IV


the current


study.


difference


the number


observed


peaks


studies


Ashwal


et al.


1984) ,


Woods and Plessinger


(1985),


and Woods et


1987


resulted


from their


studies were


can be











than


other


peaks


that


typically


constitute


ABR


(Jewett


Willi


ston,


1971).


The


esence


of repeatable


waveforms


dGA


was


several


days


earlier


than


first


response


obtained


from


utero


fetal


sheep


dGA


Woods


' group


Woods


Plessinger,


1985


diff


erence


in transducers


used


ese


studies


hearing


Woods


receiver


a bone


covered


oscillator


with

was u


rubber


sed


was

the


used


current


study


may


account


time


at whi


ch the


ABR


first


emerged.


Wolfson


et al.


(1990


were


able


identify


four


repeatable


peaks


exteriorized


fetal


sheep


dGA.


They


used


a bone


osc


illator


to deliver


click


stimulus.


However,


ABR


fetus


recording


been


was


delivered


obtained


caesarian


within


sec


30 minutes


tion


after


delivery.


premature


lambs


used


Wolf son


et al.


1990


study


were


sustained


on liquid


ventilation.


Additionally,


stimulus


levels


between


Wolfson


and


current


study


are


difficult


compare


because


methodological


variations.


Neverth


ess


, a comparison


the c

there


current

are d


findings


if ferences


Wolfson


between


findings


utero


suggest


that


ex utero


-2 I 1- 1- -


L


. .. _" _


I


A -


_Y


m










ex utero


environment,


which


could


alter


middle


ear


function


influence


ABR.


Also,


performance


bone


osc


illator


when


surrounded


fluid


clearly


differs


from


its performance


in air.


Both


factors


influence


the morphology


ABR


because


of stimulus


intensity


diff


erences


present


inner


ear.


only


ABR


waveform


morphology


change


over


time,


ABR


thresholds


also decreased


rapidly.


Figure


displays


mean


ABR


thresholds


over


time


four


stimuli


types


nonexposed


group.


Means,


standard


deviations,


minimum


maximum


thresholds


animals


can


be found


Appendix


Section


Recall


that


nHL


is referenced


to human


behavioral


sensitivity


with


bone


oscillator


placed


on the skin


overlying


mastoid.


In contrast,


bone


oscillator


on the


Thus,


fetal


etal


sheep


ABR


was


applied


thresholds


directly


dGA


skull.


above


were


found


at stimulus


levels


below


audibility


human


subjects.


Rapid


changes


threshold


occurred


stimuli


types

this


from


dGA


period,


ABR


res


dGA.

hold


example,


during

stimulus


improved


This


improvement


was


most


remark-


able


change


, but


e responses


to other


stimul


-a-


showed


v













dB nHL


40




30




20




10




0




-10




-20


1 1 1 1 1 1


33
0 1


34


dGA


El I
. -t. .. r -


-2 71flfl


4c 1^>-rla A


S4-,, n 1 l r "^lrc 1


mnrA


__J











Thresholds


continued


to de


crease


between


dGA,


but at


a rate of


approximately


0.15


dB/day.


dGA,


thresholds


kHz were


15 dB


lower than


thresholds


kHz,


and click stimuli


and


remained


so until


dGA.


that


time,


thresholds


became


poorer


to 5 dB.


136 dGA,


thresholds were


stimuli.


2-15 dB poorer than


These differences may


thresholds


be related


other


to developmental


changes


in bone-conducted ABRs.


Yang


et al.


1987)


Hooks and Weber


1984


found


infants that


latencies


bone-conducted


clicks


lower


frequency than air-conducted


clicks)


were


longer than adult


latencies.


authors


these


studies argued


that a base-to-apex developmental


gradient,


known


to occur postnatally


some


animals and


prenatally


in humans and other


animals,


could result


shorter


latencies


for undeveloped


ears.


This


same


line of


reasoning


could apply to ABR thresholds.


to low frequencies compared


to thresholds


Lower thresholds


higher


frequencies


could be a


function


development


place


principle.


Other


factors may well


have


been


involved,


including


frequency-specific changes


transduction


properties


s at


bone oscillator-skull


interface


that


favor


signal


efficiency


early


after placement


skull,


tThab r'h c~banno


-J ': I 1lU


cldii11 n


Sr- rntr c


P" -r' f;i r'r'l-i m


thhcoe











results


earlier


dGAs


were


in agreement


with


the basal


to apical


theory


of cochlear


development


Rubel


Ryals,


1983)


, i..


frequencies


are


effective


initially


during


res


clicks


time


base


development.


holds


place


Conversely,


frequency


or higher


along


frequency


basilar


code


during


stimuli


stimuli


membrane


moves


apically


maturation,


are


ABR


sensitive


because


needed


travel


frequency


stimuli


Kiang


Moxon,


1974;


Davis


Hirsh,


1979).


remaining


stimuli


types


in the


current


study,


the click


tone


burst


thresholds


were


most


similar.


Presumably,


tone


burst


cited


responses


from


fibers


more


basal


than


and


tone


be closer


to fiber


locations


whi


contribute


responses.


thresholds


stimulus


later


may


have


been


related


resonance


bone


osc


illator.


Refer


to Figure


spectra


tone


burst.


one


example,


dGA


mean


ABR


latency-intens


functions


evoked


from


the nonexposed


etuses


with


click and


tone


burst


stimuli


are


shown


Figure


3-3.


Refer


to Appendix


Section


means,


standard


deviations,


minimum


maximum


latencies


Waves


I-IV,


" 1rnna -


Im _nl Vn* lt


an i ma


Thp


11p


I. I II V 1


LJ I


filII





















0-


+--E


-7


dB nHL


-- Wave I -4 Wave II Wave III 0 Wave IV










atypical


linear


function.


However,


slope of


function was


similar


waves


both


stimuli


types.


latencies decreased between


.75 ms


decrease


in intensity.


were consistent


with


Latency


shifts of


literature


these magnitudes


from human ABR


latency-


intensity


functions.


example,


Schwartz


and Berry


1985)


reported


ms/10 dB and Rosenhamer


1981)


reported


0.01


ms/dB,


which are equal


to 0.8


0.2 ms/


0 dB,


respectively.


The


Wave


was


identified because of


length


stimulus artifact.


Also,


kHz peaks


that


are


identifiable


(Waves


III,


longer


latencies


than


the click-evoked


peaks.


Once again,


these


longer


latencies were


related


stimulus


travel


time on


basilar membrane.


only


did


thresholds decrease


rapidly


over time,


latencies decreased during


development


from 111


dGA


dGA.


In Figure


3-4,


the mean


click-evoked Wave


I-IV


latencies


for two


intensity


levels


and 21


nHL)


are


displayed.


Overall,


latencies


for the


four


identifiable


peaks decreased over


increasing GA.


These decreases


latencies


are mostly


related


increased myelination,


increased axon diameter,


ii1- fernr'h n .,* T nn I C


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greater


changes were observed


latencies


of Waves


These


findings were


in agreement


with


Wolfson


et al.


study


and a human developmental


study


by Salamy


and McKean


(1976).


Salamy


and McKean hypothesized differential


rates


of maturation between


peripheral


and central


auditory


pathways.


Another


could be


factor


related


contributing


to development


latency


of place


decrease


specificity.


study


investigating the effects


forward masking


on human


Waves


more

basal


biased by

events.


Zapala


apical


et al.


(1992)


concluded


influences while Wave


Following the


base


that


Wave


V is


reflects more


to apex developmental


course,


Wave


then


should initially


represent


the more


developed portion


the cochlea and consequently reflect


fewer


changes.


the cochlea was continuing to mature,


later waves


improve


(III


latency


IV in


sheep)


the apical


would be expected


portions


the cochlea


continued


to develop.


third consideration


for differential


rates


change


peak


latencies was


function of


supposed


generators


for Waves


the cochlear nerve,


(the distal


respectively


(Mller


proximal


et al.,


ends


1981).


the cochlea and


the cochlear portion


VIIIth


r-ani 1


nirvs wore awr


1 Pacst


nart i al v


fiincti .onal.


as thev


I











because


Wave


ency


was


short


when


was


first


identified,


was


difficult


show


as great


a decrease


latency


later


occurring


waves.


Description


of Normal


Cochleae


sheep


coc


hlea


was


striking


unusual


shape.


Most


mammals


possess


a conically-shaped


coc


hlea


with


sca


lae,


larger


at the base


smaller


apex.


coc


hlear


turns


revolve


symmetrically


around


modiolus


and


axis


modiolus


remains


about


same


plane


(Suga


Hattler,


1970;


Harrison


Hunter-Duvar,


1988).


Basilar


membrane


length


varies


with


species.


example,


are


humans,


turns


length


, whereas


is roughly


chinchillas,


mm and


there


there


are


turns


Yost


elsen,


1985).


Figure


is a photograph


opened


cochlea


obtained


from


to 5


week


lamb.


fetal


organ


of Corti


consisted


turns


(Figure


-5),


with


very


long


approximately


to 9


basal


turn


compared


ove


rall


length


approximat


mm).


axis


middle


modiolus


turn.


changes


one


abruptly


instance


between


Figure


base


a cross-


sec


tional


view


organ


of Corti


occurred


same


co ar 1


rall 1 1 n -


0 17 Orr ellnarl tre


4. hnf


A m


* ir^T


-f^sn ^a n^4


tt a










60








H..


























IIr

.iI'.
H
d.









m a






.H












I



























































Figure


3-6. Cros


s-sectional vie


w (C)


and superior view











first


same


turn.


Figure


areas,


shows


a lateral


higher


view


magnifications


organ


of Corti


superior


view


organ


of Corti.


unusual


shape


fetal


sheep


cochlea


illustrated


cochlear


reconstructions


Figure


shows


"tear-drop"


shape


obtained


fetal


sheep


subjects.


An adju


stment


to the


graphic


reconstruction


method


used


other


species


(Guild,


1921;


Schuknecht,


1953


to be made.


adjustment


was


reconstruction


modiolus


measuring


oval


shape


around


plotting


axis


distance


between


pillar


cells,


instead


using


a comp


ass


to construct


semicircles.


reconstruction


still


was


exact,


however,


because


tilt


modiolar


axis


could


measured


illustrated


from


this


type


of preparation.


Because


bend in


modiolus


fetal


sheep


cochlea,


ere


was


difficulty


in reconstructing


anatomy


traditional


serial


sectioning


method.


was


impossible


rotation


a consistent


to complete


plane


mid-modiolar


a preparation


in some


plane


without


sections.


sec


tion


artifact


In most


caused


species,


sought.


However,

proper p


when


fetal


positionn


cutting


cochlea


basal


was


blocked


sections,


the

apical


TTI Am nAJ ni rl


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When


apex


was


optimally


cut,


base


exhibited


cutting


artifact.


Experiment


Developmental


Effect


on the


ABR


purpose


of Experiment


was


to determine


whether


a noise


exposure


delivered


dGA


fetus


an effect


on the


continuing


development


ABR.


Thresholds


Figure


illustrates


mean


thresholds


four


stimulus


types


nonexposed


early


exposed


animals


various


maximum


Means,


thresholds


standard


animals


deviation


can


minimum


found


Appendix,


Section


exposure


dGA,


Following


thresholds


cessation


early


noise


noise-exposed


group


stimulus


types


were


comparable


nonexpo


group.


group


Thresholds


increase


dGA,


early


immediately


noise-exposed


after


noise


exposure.


In other


words,


ere


was


no threshold


shift.


This


finding


was


surpr.


rising


since


pre-


exposure


thresholds


were


already


high.


example,


ma n


11IT 3 I* i


nreexnnou -re


cl.i


k-evoked


threshold


was


21 dB nHL


which


j














dB nHL


1 1 1 1 1 1 1 1


dGA


-- Early Noise exposed


Nonexposed


dB nHL


1 1 1 1 1 1 1 1


dGA


..- --














dB nHL


1 11 1 1 11 1
1 11 1 2 33 3
1 34 6 3 01 6


dGA


-"- Early Noise exposed


"-- Nonexposed


dB nHL


1 11 1 1 11 1
1 11 1 2 33 3
1 34 6 3 0 1 6


dGA











In contrast


the earlier GAs,


the mean


nonexposed


thresholds


(after


dGA)


were more


sensitive


than


thresholds of


the early noise-exposed


group.


An exception


threshold


stimulus


on dGA


123.


later


GAs,


a trend


toward separation between


two groups


appeared.


Figure


3-10


illustrates


threshold


shift


between


early-exposed


group and


the nonexposed


group


stimulus


types


for various GAs.


Recall


that


the noise


exposure occurred immediately


before


dGA


measurement.


Threshold


shift


was greater


130,


and


dGAs.


These


results


indicated


that


while


there was


little


immediate


threshold effect after


noise exposure


dGA,


the ABRs


for the early noise-exposed animals


recorded


weeks


or more


subsequent


noise exhibited


higher thresholds


than nonexposed animals.


Figure


depicts


the mean ABR


thresholds


stimuli


dGA for the nonexposed,


early


and


late


noise-


exposed


groups.


This day


a preexposure measurement


late


noise-exposed animals.


A one-way


analysis


variance

threshold


revealed a


significant difference among the


three groups with an attained p-value of


0.0093.


These


findings contradicted


Dunn


et al.


1981


ayhaan '4-1-n,,r a rl A r anl


9


4 l r-hC i l rA


f^4 = i


Cl* r\ cl"^rf-y f -'


*t-l"*^














O -
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o7z
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qr






(N
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Co

CNC








I-













t)l
ca-




Sf -

0 C (0 N C e















dB nHL


2


0


-2


-4


-6


-8



-10



-12


130 dGA


Nonexposed


Early noise-exposed


Late noise-exposed


V ^ /rt,,


Ma 1DnD *1,rae,1A rl^ all e


E


iE


"s -' l l 1 1WI 1-a


1-










lambs


who


been


prenatally


exposed


dB SPL


hours/day


because


days


a week


results


for

curre


several

nt study


months.

document


However,

shifts


ABR


following


noise


exposure,


more


relevance


human


(1986).


studies


They


Dani


found


Laciak


an increased


1982


sk of


Lalande


hearing


et al.


Oss


children


whose


mothers


were


occupationally


exposed


hazardous


noise.


Lalande


study,


there


was


significant


frequency


a strong


increase


4000


component


children'


Hertz


risk


when


low-frequency


hearing


exposure


noise.


These


OSs


involved


studies


have


been


criticized


methodological


shortcomings


Henderson


al.,


1993


suC


a lack


of a matched


control


group.


Nonth


eless,


results


current


study


show


that


is possible


an exogenous


intense


exposure


have


some


effect


on hearing


sensitivity


in utero.


Latencies


Figure


3-12


contains


mean


latencies


ck-evoked


Waves


III,


IV for


nonexpos


and


early


Appendix


noise-exposed


Part


groups


, for


various


means,


GAs.


standard


Refer


deviations


minimum


maximum


latencies


Waves


I-IV,


IV N


trough,


amplitude


-- -


these


animals.


w


__


__I_


___ w -

























Figure 3-12. Mean ABR click-evoked latencie
nHL for various GAs. Differences between the non
early-noise exposed groups at 116 and 123 dGA are
significant. A. Wave I; B. Wave II; C. Wave III;
IV.


at 41
exposed
not
D. Wav


dB
and


e































1 1


dGA


Nonexposed


-i-I


Early noise-exposed


Wave


dGA


I Ii I I I I- I I I I I I I I I I


Il





























I I I I II I I I I I I I I


dGA


-"Nonexposed


-4-


Early noise-exposed


Wave III


1 1 1 1 1
1 2 3 3 3
6 3 0 1 6


dGA











130,


131,


dGAs


, this


trend


reversed


late


cies


exposed


nonexposed


groups


were


nearly


identical


Previous


adult


studi


of NIHL


ABR


described


increases


in latenci


following


noise


expo


sure


In humans


with


known


hearing


evel


s and


a positive


noise


expo


sure


history,


many


studi


(Coats


Martin,


1977;


Keith


and


Grevill


frequency'


Wave


, 1987;

y hearing


V latency


Yamada

g loss

Jerge


et al.,

prolonge

r and Jo


1979


d Wave


hnson


reported


latency


1988


that


high


greater


reported


than


that


human


Oss


days


Wave


increase


following


V latency


beyond


noise


increased


as high


to 60


exposure


-frequency


this


Waves


study,


through


hearing


a few


IV latenci


were


no longer


noise


-exposed


group.


Experiment


Two


Early


Versus


Late


Exposure


Effects


on the


ABR


purpose


experiment


was


to determine


whether


intense


noise


delivered


an earli


dGA


fetus


create


a change


in the


auditory


stem


which


differed


from


a noise


deli


vered


to a later


(130


dGA


fetus.


mk...-ankal An











age-matched measurements


for the nonexposed animals,


can be


found


in the Appendix,


Section A.


Figure


3-13


illustrates


mean


thresholds


for these


three groups


for the


four


stimulus


types.


The


late noise-exposed group showed a


postexposure


increase


in threshold followed by a decrease


in threshold


referred to as

average thresho


recovery for all


stimuli.


to click stimuli


The


increase


between


the pre-


exposure and postexposure recordings was significant with an


attained p-value of


and


0.0062.


Thresholds evoked by the


tone bursts showed the


same


kHz,


pattern


increased


thresholds


postexposure


followed


a recovery


decrease


in threshold,


these


postexposure


increases


were


significant.


These


using

shift


findings


other sp

to click


ecies


stimuli


are consistent with


other NIHL studies,


indicate a small ABR threshold


after noise exposure


(Attias et al


1990;


Hildesheimer


et al


. 1991).


Attias et al.


reported a


temporary


increase


in rat ABR thresholds


following


hour


exposure to


115 dB SPL noise.


Two weeks after


exposure,


thresholds


returned


their preexposure


level.


In a


study


evaluating the


possible


interaction of


sedation and NIHL


guinea


pigs,


Hildesheimer


et al.


reported


temporary threshold


shift


the action potential


following


exposure


to a


minute.


- - -. F-.-


pure tone at


120 dB SPL.


I


_ _

























thres
and 1
stimu
kHz s


Figure
holds f
ate noi
lus. B
timulus


3-13. Mean pre- and postexposure and r
or the nonexposed, early noise-exposed
se-exposed (130 dGA) groups. A. Click
. 2 kHz stimulus. C. 1 kHz stimulus.
.


recovery
(113 dGA)















dB nHL


Pre-Exposure Post-Exposure Recovery


Condition


Nonexposed


Early Noise-Exposed


-1- Late


Noise-Exposed


= 0.0062


dB nHL


Pre-Exposure Post-Exposure Recovery


Condition


Next


Next















dB nHL


Pre-Exposure Post-Exposure Recovery


Condition


Nonexposed


- Eady Noise-Exposed


-- iLate Nolse-Exposed


dB nHL


Pre-Exposure Post-Exposure Recovery


Condition


Next


Next










frequency


ABR thresholds


the more developed


fetus


were


as sensitive


as clicks


or the


higher


frequency


stimuli,


because


increased


frequency


travel


time


along the


ilar membrane


(Kiang


and Moxon,


1974;


Davis


and Hirsh,


1979) .


An alternative view could be


that


the noise


effect


was


biased


toward


high


frequency


basal


cochlea.


Thresholds


for the early noise-exposed


group did not


increase after the


exposure


stimulus type.


fact,


thresholds


immediately


after noise exposure decreased at


nearly the


same


rate as


for the


nonexposed


group.


lack


of a threshold


seem unusual


Poor


change


for the early noise-exposed


because of


sensitivity


the poor preexposure


stimulus


group did


thresholds.


types would have made


threshold changes difficult


sensitivity


to detect.


late noise-exposed


improved


group made changes


thresholds more


likely to occur


and easier


to detect.


separation between


the mean nonexposed


thresholds


the mean


early noise-exposed


thresholds


kHz was


recording


unusual


and may be a reflection


ABR responses to


low frequency


the difficulty


stimuli.


moderate


to high


intensity


levels,


there


spread


energy


along the


basilar membrane causing


a low


frequency


stimulus to


exc:


ite a hi aher


f reauencv


area


I


Goraa


et all.











among


animal


tone


burst


stimuli


would


expect


mean


preexpo


sure


there


sholds


each


ese


stimulus


types


to have


been


similar


standard


deviations


are


there


somewhat


sholds


the 0


greater


Refer


tone


than


those


to Appendix


ck and


Section


A for


esholds

kHz


standard


deviations


Latenci


Appendix


Section


B contains


means,


standard


deviations,


IV N


minimum


trough,


maximum


amplitude


latenci


Waves


nonexpos


early


-IV,


and


late


noise


-exposed


animal


Recall


that


latency


measurements


were


available


in the


nonexpos


and


early-


exposed


groups


until


dGA.


Consequently,


early


noise


-exposed


group,


there


are


no pre-


postexposure


latenci


to consider


between


dGAs.


Figure


latency


illu


differences


states


dGA


for

131


all

minus


groups tn

dGA 130.


click-evoked

For the


late


-exposed


group,


ese


differences


represent


pre-


and


post-noise


expo


sure


means


urements


. If


the ABR


recordings


from


ese


difference


days


would


been


have


same,


een


When


the expected


compared


ency


late


nni ?,_


nrninn -


n I I I I


riand


Par1 v


-

Wa\7ia<=


nnnn nYr


n




















Figure 3
dGA 131 minus
noise-exposed
for Waves II,
three groups


-14. Mean click-
dGA 130 for the
animals. Signif
III, and IV at 4
are designated by


evoked
nonexpo
icant d
1 and 2
asteri


latency
sed, ear
ifferenc
1 dB nHL
sks.


differences
ly and late
es (p < .05
among the