?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=https%3A%2F%2Fdoktori.bibl.u-szeged.hu%2Fid%2Feprint%2F10834%2F&rft.title=NMDA-+and+asphyxia+induced+alterations+of+neurovascular+responses+in+the+cerebral+cortex+of+newborn+pigs%2C+implications+for+the+pathomechanism+of+neonatal+hypoxic-ischemic+encephalopathy&rft.creator=+Remzs%C5%91+G%C3%A1bor&rft.subject=03.01.+%C3%81ltal%C3%A1nos+orvostudom%C3%A1ny&rft.description=Perinatal+asphyxia+(PA)+is+a+major+cause+of+neonatal+mortality+and+it+can+also+lead+to+hypoxic-ischemic+encephalopathy+(HIE)+in+the+surviving+newborns.+Despite+the+availability+of+therapeutic+hypothermia%2C+HIE+still+results+in+long+term+disability+in+many+infants%2C+as+hypothermia+alone+is+often+not+sufficient+to+fully+mitigate+the+HIE+caused+neuronal+damage.+To+find+new+adjunct+therapies%2C+further+investigation+of+the+neuronal+and+vascular+pathomechanisms+underlying+HIE+development+is+warranted%2C+and+the+newborn+pig+used+in+our+studies+is+one+of+the+best+large+animal+model+for+the+preclinical+translational+study+of+PA%2FHIE.%0D%0ATo+enhance+the+mechanistic+understanding+of+neuronal+injury+in+our+previously+established+translationally+valid+PA%2FHIE+model%2C+first+we+aimed+to+determine+the+magnitude%2C+the+dynamics%2C+and+the+mechanisms+of+PA+on+the+brain+interstitial+pH+(pHbrain)+both+during+asphyxia+and+HIE+development.+Second%2C+we+investigated+the+effects+of+excessive+glutamatergic+activation+by+NMDA+on+neurovascular+unit+function+using+hypercapnia+induced+vasodilation+to+test+cerebrovascular+reactivity.+Third%2C+we+wanted+to+explore+if+NMDA+could+alter+both+the+spontaneous+and+also+the+hypercapnia+induced+changes+in+cortical+electrical+activity.+%0D%0AAnesthetized+and+mechanically+ventilated+piglets+were+fitted+with+either+open+or+closed+cranial+windows.+pHbrain%2C+cortical+blood+flow+(CoBF)%2C+and+neuronal+activity+was+determined%2C+with+pH+sensitive+microelectrodes%2C+laser-speckle+contrast+imaging%2C+and+multi-channel+intracortical+microelectrodes%2C+respectively.++PA+was+elicited+by+ventilation+with+a+hypoxic-hypercapnic+gas+mixture+(6%25O2%2C+20%25CO2%3B+20min)%2C+then+HIE+development+was+observed+up+to+24h.+NMDA+was+applied+onto+the+cortical+surface%2C+graded+(5-20%25)+hypercapnia+was+induced+by+ventilation+with+a+normoxic-hypercapnic+gas+mixture.%0D%0ApHbrain+dropped+below+6.0+during+PA+exceeding+by++~0.8+pH+unit+the+acidosis+in+the+blood+highlighting+its+importance+in+neuronal+injury.+The+respiratory+component+was+responsible+for+only+~40%25+of+the+developing+acidosis.+pHbrain+was+restored+quickly+after+PA+and+remained+stable+throughout+the+observation+period.+Both+graded+hypercapnia+and+NMDA+caused+increases+in+CoBF%2C+but+NMDA+also+attenuated+the+response+to+hypercapnia+in+an+NMDA-receptor+and+nitric+oxide+synthase+(nNOS)+dependent+manner+shown+with+respective+inhibitors.+NMDA+induced+neurovascular+dysfunction+was+also+shown+by+NMDA+induced+perturbations+in+cortical+neuronal+activity+and+the+altered+electrophysiological+response+to+graded+hypercapnia+as+well.%0D%0AOur+findings+suggest+that+severe+acidosis+as+well+as+excitotoxic+neurovascular+unit+dysfunction+may+play+an+important+role+in+PA%2FHIE+pathpohysiology+in+our+translational+PA%2FHIE+model.&rft.date=2021-06-24&rft.type=Disszert%C3%A1ci%C3%B3&rft.type=NonPeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=https%3A%2F%2Fdoktori.bibl.u-szeged.hu%2Fid%2Feprint%2F10834%2F1%2FRemzsoG_Dissertation.pdf&rft.format=application%2Fpdf&rft.language=en&rft.identifier=https%3A%2F%2Fdoktori.bibl.u-szeged.hu%2Fid%2Feprint%2F10834%2F2%2FRemzsoG_short_thesis.pdf&rft.format=application%2Fpdf&rft.language=hu&rft.identifier=https%3A%2F%2Fdoktori.bibl.u-szeged.hu%2Fid%2Feprint%2F10834%2F3%2FRemzsoG_tezisfuzet.pdf&rft.identifier=+++Remzs%C5%91+G%C3%A1bor%0A+++NMDA-+and+asphyxia+induced+alterations+of+neurovascular+responses+in+the+cerebral+cortex+of+newborn+pigs%2C+implications+for+the+pathomechanism+of+neonatal+hypoxic-ischemic+encephalopathy.%0A++Doktori+%C3%A9rtekez%C3%A9s%2C+Szegedi+Tudom%C3%A1nyegyetem+(2000-).+%0A(2021)+++++&rft.language=eng