Ultrastructural observation of effect of moderate hypothermia on axonal damage in an animal model of diffuse axonal injury

(整期优先)网络出版时间:2002-06-16
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Objective:Toinvestigatetheeffectofmoderatehypothermiaonresponsesofaxonalcytoskeletontoaxonalinjuryintheacutestageofinjury.Methods:Offifteenadultguineapigs,twelveanimalsweresubjectedtostretchinjurytotherightopticnervesandpidedintothenormothermicgroup(n=6)inwhichtheanimal'scoretemperaturewasmaintainedat36.0-37.5℃andthehypothermiagroup(n=6)inwhichthecoretemperaturewasreducedto32.0-32.5℃afterstretchinjury.Remainingthreeanimalssustainednoinjurytotherightopticnervesandservedascontrolgroup.Halfofinjuredanimals(n=3)ofeithernormothermicgrouporhypothermicgroupwerekilledateither2hoursor4hoursafterinjury.Theultrastructuralchangesofaxonalcytoskeletonoftherightopticnervefibersfromtheanimalswereexaminedunderatransmissionelectronmicroscopeandanalyzedbyquantitativeanalysiswithacomputerimageanalysissystem.Results:At2hoursafterstretchinjury,therewasasignificantreductioninthemeannumberofmicrotubules(P<0.001),andasignificantincreaseinthemeanintermicrotubulespacing(P<0.05orP<0.01)inaxonsofallsizesinnormothermicanimals.Themeannumberofneurofilamentsalsodecreasedstatistically(P<0.01)inlargeandmediumsubgroupsofaxonsinthesameexperimentalgroupat2hours.By4hours,thelargesubgroupofaxonsinnormothermicanimalsstilldemonstratedasignificantdeclineinthemeannumberofmicrotubules(P<0.01)andanincreaseinthemeanintermicrotubulespacing(P<0.05),whilethemediumandsmallsubgroupsofaxonsdisplayedasignificantincreaseinthemeannumberofneurofilaments(P<0.05)andreductioninthemeaninterneurofilamentspacing(P<0.05).Onthecontrary,eitherthemeannumberofmicrotubulesandthemeanintermicrotubulespacing,orthemeannumberofneurofilamentsandinterneurofilamentspacinginaxonsofallsizesinhypothermicstretch-injuredanimalswasnotsignificantdifferentfromthemeanvaluesofsham-operated