AN ANIMAL-MODEL OF HYPOXIA-INDUCED PERINATAL SEIZURES

Clinically, neonatal hypoxic encephalopathy is commonly associated wit h seizure activity. Here we describe a rodent model of cerebral hypoxi a in which there is are age dependent effects of hypoxia, with hypoxia inducing seizure activity in the immature vat, but not in the adult. Global hypoxia (3-4% O-2) induced acute seizure activity during a wind ow of development between postnatal day (P5-17), peaking at P10-12. An imals which had been rendered hypoxic between P10-12 had long term dec reases in seizure threshold, while animals exposed at younger (P5) or older (P60) ages did not. Antagonists of excitatory amino acid (EAA) t ransmission appear to be superior to benzodiazepines in suppressing th e acute and long term effects of perinatal hypoxia, suggesting involve ment of the EAA system in these phenomena. No significant histologic d amage occurs in this model, suggesting that functional alterations tak e place in neurons when exposed to an hypoxic insult at a critical dev elopmental stage. Future work is directed at evaluating molecular and cellular events underlying the permanent increase in seizure susceptib ility produced by this model.