An animal model of hypoxia-induced perinatal seizures.

Clinically, neonatal hypoxic encephalopathy is commonly associated with seizure activity. Here we describe a rodent model of cerebral hypoxia in which there is are age dependent effects of hypoxia, with hypoxia inducing seizure activity in the immature rat, but not in the adult. Global hypoxia (3-4% O2) induced acute seizure activity during a window of development between postnatal day (P5-17), peaking at P10-12. Animals which had been rendered hypoxic between P10-12 had long term decreases in seizure threshold, while animals exposed at younger (P5) or older (P60) ages did not. Antagonists of excitatory amino acid (EAA) transmission appear to be superior to benzodiazepines in suppressing the acute and long term effects of perinatal hypoxia, suggesting involvement of the EAA system in these phenomena. No significant histologic damage occurs in this model, suggesting that functional alterations take place in neurons when exposed to an hypoxic insult at a critical developmental stage. Future work is directed at evaluating molecular and cellular events underlying the permanent increase in seizure susceptibility produced by this model.