1. ¹Department of Pediatrics, Oregon Health and Sciences University, Portland, Oregon, USA
2. ²Department of Neurology, Oregon Health and Sciences University, Portland, Oregon, USA
3. ³The Center for Research on Environmental Toxicology, Oregon Health and Sciences University, Portland, Oregon, USA
4. ⁴Behavioral Neuroscience, Oregon Health and Sciences University, Portland, Oregon, USA
5. ⁵Veteran Affairs Medical Center, Portland, Oregon, USA
6. ⁶The Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK

Correspondence: Dr R Fern, Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, University Road, Leicester, LE1 9HN, UK. E-mail: rf34@leicester.ac.uk

Received 11 November 2005; Revised 21 April 2006; Accepted 28 April 2006; Published online 7 June 2006.

Abstract

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 (2.130.25 counts/m²), and declined significantly during hypoxia–ischemia (0.930.15 counts/m²: P<0.001). Astrocytes had lower glutamate levels (0.70.07 counts/m²), and showed a relatively small decline during hypoxia–ischemia. Axonal regions contained high levels of glutamate (1.840.20 counts/m²), much of which was lost during hypoxia–ischemia (0.720.20 counts/m²: 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 (1.900.20 counts/m²), and ependymal cells (2.200.28 counts/m²), and hypoxia–ischemia produced a large fall in ependymal glutamate (0.970.08 counts/m²: P>0.001). The ependymal cells were damaged by the insult and represent a further potential source of glutamate during ischemia.