EFFECT OF HYPOXIA-ISCHEMIA ON BICUCULLINE-INDUCED SEIZURES IN IMMATURE RATS - BEHAVIORAL AND ELECTROCORTICAL PHENOMENA

The relation between hypoxia/ischemia and subsequent alterations in seizure susceptibility in developing brain remains unclear. We assessed the behavioral and electrocorticographic (ECoG) effects of hypoxic/ischemic brain damage on bicuculline (BIC)-induced seizures in 7-day postnatal rats, and determined maturational changes in seizure susceptibility, behavior and ECoG activity. Rat pups were subjected to unilateral common carotid artery ligation, followed by exposure to 8% O-2 at 37 degrees C for 2 h, an insult that produces brain damage in the cerebral hemisphere ipsilateral to carotid artery occlusion. The experimental group consisted of rat pups previously subjected to hypoxia/ischemia; control littermates received neither arterial ligation nor systemic hypoxia. Experimental animals received 4, 5, or 6 mg/kg BIC subcutaneously (s.c.) at 2 and 24 h, and at 3, 7, and 21 days of recovery from hypoxia/ischemia. Two animals at each interval of recovery, 1 each from the experimental and control groups, were used for ECoG monitoring. After BIC injection, animal behavior was observed for 2 h. Behaviors and seizures were classified in five categories based on severity, duration, and character: 1, mild irritability; 2, few clonic seizures and agitation; 3, few tonic-clonic seizures with swimming movements; 4, frequent tonic-clonic seizures with apneic episodes; 5, continuous tonic-clonic seizures and death. Rat pups previously subjected to hypoxia/ischemia had lesser seizure susceptibility than controls at 2-h recovery (p < 0.05) and greater susceptibility than controls at 24 h (p < 0.05), Tonic seizures were prominent at 2 and 24 h in both the experimental and control groups, whereas lesion-sided circling was prominent only in the hypoxic/ischemic rat pups, At 3 days of recovery, seizure susceptibility was greater in controls (p < 0.05), decreasing thereafter through 21 days of age. No significant differences in seizure severity were noted between the 2 groups at 7 and 21 days, A close correlation existed between behaviorally observed seizures and ECoG paroxysmal activity in all groups, although low-amplitude spike activity occurred without associated behavioral changes, especially at 2 and 24 h of recovery. Hypoxia/ischemia severe enough to produce brain damage probably initially suppresses seizure susceptibility, which thereafter is temporarily increased at 24 h of recovery. The age-dependent changes in seizure susceptibility after hypoxia/ischemia presumably relate to injury-induced imbalance between excitatory and inhibitory neurotransmitter systems.