Hypoxia-ischemia preferentially triggers glutamate depletion from oligodendroglia and axons in perinatal cerebral white matter

Stephen A. Back, Andrew Craig, Robert J. Kayton, Ning Ling Luo, Charles K. Meshul, Natalie Allcock, Robert Fern

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Ischemia is implicated in periventricular white matter injury (PWMI), a lesion associated with cerebral palsy. PWMI features selective damage to early cells of the oligodendrocyte lineage, a phenomenon associated with glutamate receptor activation. We have investigated the distribution of glutamate in rat periventricular white matter at post-natal day 7. Immuno-electron microcopy was used to identify O4(+) oligodendroglia in control rats, and a similar approach was employed to stain glutamate in these cells before and after 90 mins of hypoxia-ischemia. This relatively brief period of hypoxia-ischemia produced mild cell injury, corresponding to the early stages of PWMI. Glutamate-like reactivity was higher in oligodendrocytes than in other cell types (2.13±0.25 counts/μm2), and declined significantly during hypoxia-ischemia (0.93±0.15 counts/μm2: P<0.001). Astrocytes had lower glutamate levels (0.7±0.07 counts/μm 2), and showed a relatively small decline during hypoxia-ischemia. Axonal regions contained high levels of glutamate (1.84±0.20 counts/μm2), much of which was lost during hypoxia-ischemia (0.72±0.20 counts/μm2: P>0.001). These findings suggest that oligodendroglia and axons are the major source of extracellular glutamate in developing white matter during hypoxia-ischemia, and that astrocytes fail to accumulate the glutamate lost from these sources. We also examined glutamate levels in the choroid plexus. Control glutamate levels were high in both choroid epithelial (1.90±0.20 counts/μm2), and ependymal cells (2.20±0.28 counts/μm2), and hypoxia-ischemia produced a large fall in ependymal glutamate (0.97±0.08 counts/μm2: P>0.001). The ependymal cells were damaged by the insult and represent a further potential source of glutamate during ischemia.

Original languageEnglish (US)
Pages (from-to)334-347
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number2
StatePublished - Feb 2007


  • Axon
  • Choroid plexus
  • Glutamate
  • Ischemia
  • Oligodendrocyte
  • White matter

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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