Acute and chronic effects of hypoxia on the developing hippocampus.

Abstract

Perinatal hypoxia is associated with both seizures arising acutely and the subsequent development of temporal lobe epilepsy (as determined retrospectively). We therefore attempted to identify acute and chronic morphological and/or electrophysiological hippocampal pathologies associated with experimentally induced hypoxia in immature rats. Pups were exposed to 15 minutes of hypoxia on 3 successive days (starting on postnatal day 8; P8), or to 60 minutes of hypoxia on P10 with either one or multiple hypoxia-induced seizures. For animals experiencing multiple seizures, flurothyl seizure threshold was significantly lower than that of controls at 60 to 80 days, but not at 10 days, after hypoxia. Acutely, there was a treatment-related increase in the number and the density of pyknotic dentate and hilar neurons, in particular in animals experiencing multiple seizures. However, 60 to 80 days after the multiple-seizure protocol, the number of dentate and hilar neurons did not differ between control and experimental animals. Electrophysiological measures of pyramidal cell properties showed no striking difference between experimental and control animals at any time point. These results indicate that early postnatal hypoxia and hypoxia-induced seizure episodes decrease seizure threshold in the adult but produce minimal acute or chronic morphological or functional changes in the hippocampus.