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 (2.13+/-0.25 counts/microm(2)), and declined significantly during hypoxia-ischemia (0.93+/-0.15 counts/microm(2): P<0.001). Astrocytes had lower glutamate levels (0.7+/-0.07 counts/microm(2)), and showed a relatively small decline during hypoxia-ischemia. Axonal regions contained high levels of glutamate (1.84+/-0.20 counts/microm(2)), much of which was lost during hypoxia-ischemia (0.72+/-0.20 counts/microm(2): 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/microm(2)), and ependymal cells (2.20+/-0.28 counts/microm(2)), and hypoxia-ischemia produced a large fall in ependymal glutamate (0.97+/-0.08 counts/microm(2): P>0.001). The ependymal cells were damaged by the insult and represent a further potential source of glutamate during ischemia.

Highlights

  • Periventricular white matter injury (PWMI) is the leading cause of cerebral palsy and chronic neuro-2005; Baud et al, 2004a; Bernardo et al, 2003; susceptibility of the perinatal brain to excitotoxicHaynes et al, 2003), and with the expression of injury during ischemia is associated with aCa2 + -permeable non-N-methyl-D-aspartate (NMDA)- preferential loss of glutamate staining from oligotype glutamate receptors on the somata (Fern and dendroglia and axons with no increase in stainingMoller, 2000; Follett et al, 2000; Wilke et al, 2004). within astrocytes.Recent findings have revealed that the processes of immature oligodendrocytes express NMDAtype glutamate receptors that mediate early

  • Axonal regions contained high levels of glutamate (1.8460.20 counts/lm2), much of which was lost during hypoxia–ischemia (0.7260.20 counts/lm2: 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

  • Since we found that ligation of the carotid artery can Activation of ionotropic glutamate receptors on result in suboptimal fixation of the ischemic cerebral oligodendroglial cells during ischemia requires an hemisphere, the left common carotid artery was reversibly elevation in extracellular glutamate that must be ligated in Sprague–Dawley rat pups at P7 operated under associated with net glutamate loss from at least one isoflurane anesthesia

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Summary

Introduction

Periventricular white matter injury (PWMI) is the leading cause of cerebral palsy and chronic neuro-2005; Baud et al, 2004a; Bernardo et al, 2003; susceptibility of the perinatal brain to excitotoxicHaynes et al, 2003), and with the expression of injury during ischemia is associated with aCa2 + -permeable non-N-methyl-D-aspartate (NMDA)- preferential loss of glutamate staining from oligotype glutamate receptors on the somata (Fern and dendroglia and axons with no increase in stainingMoller, 2000; Follett et al, 2000; Wilke et al, 2004). within astrocytes.Recent findings have revealed that the processes of immature oligodendrocytes express NMDAtype glutamate receptors that mediate early. The similarities between the oligodendroglial cells Localization of Glutamate-Like Reactivity to Axons and the O4( + ) cells included numerous mitochondria, a narrow bore endoplasmic reticulum that was Axons within the white matter layer adjacent to the usually studded with ribosomes and the character- subventricular zone were generally small in diaistic nature of the chromatin distribution in the meter and were closely packed and aligned together medium and dark cells (compare Figures 2 and 3).

Results
Conclusion

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