Perinatal hypoxia-ischemia induces apoptotic and excitotoxic death of periventricular white matter oligodendrocyte progenitors

Hypoxia-ischemia (HI) is a leading cause of white matter damage, a major co ntributor to cerebral palsy in premature infants. Preferential white matter damage is believed to result from vulnerability of the immature oligodendr ocyte (the pro-OL) to factors elevated during ischemic damage, such as oxyg en free radicals and glutamate. In order to determine whether pro-OLs under go apoptotic death after HI, we analyzed periventricular white matter OLs i n P7 rats 4, 12 and 24 h after HI to analyze the time course and mode of ce ll death. DNA fragmentation was seen at 12 and 24 h of recovery after HI, r epresenting a 17-fold increase over control. In addition, caspase-3 activat ion was found in NG2+ pro-OLs at 12 h. Electron-microscopic analysis of cel l death in the white matter revealed a transition from early necrotic death s to hybrid cell deaths to classical apoptosis between 4 and 24 h of recove ry from HI. The delayed time course of apoptosis in pro-OLs supports the fe asibility of interventions to improve clinical outcomes for newborns surviv ing birth asphyxia. Copyright (C) 2001 S. Karger AG, Basel.