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

Jennifer K. Ness, Michael J. Romanko, Raymond P. Rothstein, Teresa L. Wood, Steven W. Levison

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalDevelopmental Neuroscience
Volume23
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

Keywords

  • Apoptosis
  • Caspases
  • Cell death
  • Cerebral palsy
  • Neuroglia
  • Oligodendrocytes
  • Rats
  • Stroke

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