Local cerebral blood flow in the brain during bicuculline‐induced seizures and the modulating influence of inhibition of prostaglandin synthesis

Abstract

The purpose of this study was to measure changes in local cerebral blood flow (1‐CBF) during generalized seizures, and to study whether or not formation of prostaglandins or related substances contributes to the increased flow rates. Seizures were induced in ventilated rats maintained on 70% N₂O and 30% O₂ by the i. v. injection of the GABA receptor blocker bicuculline (1.2 mg‐kg^‐1). Formation of prostaglandins was inhibited by the administration of the fatty acid cyclo‐oxygenase inhibitor indomethacin (10 mg · kg^‐1)‐Local CBF in 21 defined brain structures was measured autoradiographically with ^HC‐iodoantipyrine as the diffusible tracer. After 20 min of continuous seizure activity 1‐CBF increased 1.5‐5‐fold, the smallest increases (400% of control) in substantia nigra, thalamus, visual cortex, lateral geniculate and hypothalamus. In general, the largest increases in 1‐CBF occurred in sensory and limbic systems (and hypothalamus) while motor systems showed a pronounced variability. In the majority of structures examined indomethacin failed to modify the CBF response during seizures. Although this result suggests that seizures, in contrast to hypercapnia, lead to an increased CBF by other mechanisms than those related to prostaglandin formation, some structures (nucleus ruber, cerebellum, and superior colliculus) showed a clearly reduced 1‐CBF in indomethacin‐treated animals.