HYPOXIA-INDUCED HYPEREXCITABILITY IN-VIVO AND IN-VITRO IN THE IMMATURE HIPPOCAMPUS

Hypoxia is the most common cause of neonatal seizures and encephalopat hy. We have previously developed an in vivo experimental model of peri natal hypoxia which exhibits age-dependent acute and chronic epileptog enic effects. Between postnatal day (P) 10-12, the rat exhibits acute seizure activity during global hypoxia, while no seizures are induced at earlier (P5) or older (P60) ages. Rats exposed to hypoxia between P 10-12 have reduced seizure thresholds to chemical convulsants in adult hood. The nonNMDA antagonist NBQX appears to suppress both the acute a nd long term epileptogenic effects of hypoxia. The age-dependency of t he hyperexcitable response to hypoxia in vivo can be reproduced in vit ro using hippocampal slices. In Mg2+-free media, hypoxia induced ictal discharges within 60 s of onset in 79% of slices from normal P10 rat pups compared to 11% of adult slices (p < 0.01). Model systems such as that described here allow for correlation of in vitro and in vivo ele ctrophysiology and should provide data regarding the pharmacological a nd physiological characteristics of hypoxia-induced seizure activity i n the immature brain which could ultimately be applied to therapeutic strategies.