Effect of Hypoxia/Ischemia on Bicuculline‐Induced Seizures in Immature Rats: Behavioral and Electrocortical Phenomena

Oguz Cataltepe, Todd F. Barron, Daniel F. Heitjan, Robert C. Vannucci, Javad Towfighi

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Summary The relation between hypoxidischemia and subsequent alterations in seizure susceptibility in developing brain remains unclear. We assessed the behavioral and electrocorticographic (ECoG) effects of hypoxicl 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% O2 at 37°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 hypoxidischernia; 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 hypoxidischemia. 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 tonicclonic seizures with swimming movements; 4, frequent tonic‐clonic seizures with apneic episodes; 5, continuous tonic‐clonic seizures and death. Rat pups previously subjected to hypoxidischernia 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 hypoxia/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 hypoxidischemia presumably relate to injury‐induced imbalance between excitatory and inhibitory neurotransmitter systems.

Original languageEnglish (US)
Pages (from-to)396-403
Number of pages8
JournalEpilepsia
Volume36
Issue number4
DOIs
StatePublished - Apr 1995

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Keywords

  • Bicuculline
  • Hypoxia/ischemia
  • Immaturity
  • Rats
  • Seizures

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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