Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups 英文参考文献.docVIP

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Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups 英文参考文献.doc

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Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups 英文参考文献

Early-LifeStressIsAssociatedwithGender-Based VulnerabilitytoEpileptogenesisinRatPups Se′bastienDesgent1,2*,SandraDuss1,NathalieT.Sanon1,PabloLema1,MaximeLe′vesque1, DavidHe′bert1,Rose-MarieRe′billard1,KarineBibeau1,Miche`leBrochu1,2,LionelCarmant1,2 * 1CentredeRechercheduCentreHospitalierUniversitaireSainte-Justine,Universite′ deMontre′al, Montre′al,Que′bec,Canada,2De′partement dePhysiologie,Faculte′ de Me′decine,Universite′ deMontre′al, Montre′al,Que′bec,Canada Abstract Duringdevelopment,theriskofdevelopingmesialtemporallobeepilepsy(MTLE)increaseswhenthedevelopingbrainis exposed to more than one insult in early life. Early life insults include abnormalities of cortical development, hypoxic- ischemic injury and prolonged febrile seizures. To study epileptogenesis, we have developed a two-hit model of MTLE characterized by two early-life insults: a freeze lesion-induced cortical malformation at post-natal day 1 (P1), and a prolongedhyperthermicseizure(HS)atP10.Asearlylifestressorsleadtosexualdimorphisminbothacuteresponseand long-termoutcome,wehypothesizedthatourmodelcouldleadtogender-baseddifferencesinacutestressresponseand long-termriskofdevelopingMTLE.Maleandfemalepupsunderwentafreeze-lesioninducedcorticalmicrogyrusatP1and were exposed to HS at P10. Animals were monitored by video-EEG from P90 to P120. Pre and post-procedure plasma corticosteronelevelswereusedtomeasurestressresponseatP1andP10.Toconfirmtheroleofsexsteroids,androgenized female pups received daily testosterone injections to the mother pre-natally and post-natally for nine days while undergoingbothinsults.WedemonstratedthatafterbothinsultsfemalesdidnotdevelopMTLEwhileallmalesdid.This correlatedwithariseincorticosteronelevelsatP1followingthelesioninmalesonly.Interestingly,allandrogenizedfemales showed a similar rise in corticosterone at P1, and also developed MTLE. Moreover, we found that the cortical lesion significantly decreased the latency to generalized convulsion during hyperthermia at P