title: Perinatal hypoxia-ischemia induces apoptotic and excitotoxic death of periventricular white matter oligodendrocyte progenitors.
abstract: Hypoxia-ischemia (HI) is a leading cause of white matter damage, a major contributor to cerebral palsy in premature infants. Preferential white matter damage is believed to result from vulnerability of the immature oligodendrocyte (the pro-OL) to factors elevated during ischemic damage, such as oxygen free radicals and glutamate. In order to determine whether pro-OLs undergo apoptotic death after HI, we analyzed periventricular white matter OLs in P7 rats 4, 12 and 24 h after HI to analyze the time course and mode of cell death. DNA fragmentation was seen at 12 and 24 h of recovery after HI, representing a 17-fold increase over control. In addition, caspase-3 activation was found in NG2+ pro-OLs at 12 h. Electron-microscopic analysis of cell death in the white matter revealed a transition from early necrotic deaths to hybrid cell deaths to classical apoptosis between 4 and 24 h of recovery from HI. The delayed time course of apoptosis in pro-OLs supports the feasibility of interventions to improve clinical outcomes for newborns surviving birth asphyxia.
authors.affiliation: Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey, Pa 17033, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Ness
authors.forename: M J
authors.initials: MJ
authors.lastname: Romanko
authors.forename: R P
authors.initials: RP
authors.lastname: Rothstein
authors.forename: T L
authors.initials: TL
authors.lastname: Wood
authors.forename: S W
authors.initials: SW
authors.lastname: Levison
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002547:Cerebral Palsy / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D008854:Microscopy, Electron; D009498:Neurotoxins; D009836:Oligodendroglia / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D009498:Neurotoxins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases