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Journal of Neuroscience, Vol 9, 1693-1700, Copyright © 1989 by Society for Neuroscience
Hypobaric-ischemic conditions produce glutamate-like cytopathology in infant rat brain
C Ikonomidou, MT Price, JL Mosinger, G Frierdich, J Labruyere, KS Salles and JW Olney
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110.
We present a new animal model of perinatal hypoxic/ischemic brain damage
and compare this type of brain damage with the excitotoxic type of damage
previously described in the brains of infant rats and monkeys treated
systemically with glutamate (Glu). Ten-d-old rats with unilateral occlusion
of the common carotid artery were subjected to hypobaric conditions for 75
min and sacrificed 0-4 hr later for light and electron microscopic brain
examination. The mortality rate was relatively low (12%), and brain damage
was evident ipsilateral to the ligated carotid in 94% of surviving animals
4 hr after termination of the hypobaric event. Regions most frequently
affected were the medial habenulum, dentate gyrus, caudate nucleus,
frontoparietal neocortices, olfactory tubercle, and several thalamic
nuclei. The acute cytopathological changes, primarily edematous
degeneration of neuronal dendrites and cell bodies, evolved very rapidly,
with some neurons manifesting end-stage necrosis at 0 hr (immediately after
hypobaric exposure) and others developing such changes over a 1-4-hr
period. We conclude that the neurodegenerative reaction induced in infant
rat brain by hypoxia/ischemia is indistinguishable from the excitotoxic
type of damage exogenous Glu is known to cause. Moreover, in a companion
study (Olney et al., 1989) we show that MK-801, a powerful antagonist of
the N-methyl-D-aspartate receptor complex (subtype of Glu receptor),
protects against neuronal degeneration in this hypobaric/ischemic model.
Our results reinforce other recent evidence suggesting that
hypoxic/ischemic brain damage is mediated by endogenous Glu or related
excitotoxins.
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