Cerebral blood flow changes during pilocarpine-induced status epilepticus activity in the rat hippocampus.

Abstract

INTRODUCTION: There is a known relationship between convulsive status epilepticus (SE) and hippocampal injury. Although the precise causes of this hippocampal vulnerability remains uncertain, potential mechanisms include excitotoxicity and ischaemia. It has been hypothesised that during the early phase of seizures, cerebral blood flow (CBF) increases in the cortex to meet energy demand, but it is unclear whether these compensatory mechanisms occur in the hippocampus. In this study we investigated CBF changes using perfusion MRI during SE in the pilocarpine rat. METHODS: First, we determined whether SE could be induced under anaesthesia. Two anaesthetic protocols were investigated: isoflurane (n=6) and fentanyl/medetomidine (n=7). Intrahippocampal EEG electrodes were used to determine seizure activity and reflex behaviours were used to assess anaesthesia. Pilocarpine was administered to induce status epilepticus. For CBF measurements, MRI arterial spin labelling was performed continuously for up to 3h. Either pilocarpine (375 mg/kg) (n=7) for induction of SE or saline (n=6) was administered. Diazepam (10mg/kg) was administered i.p. 90 min after the onset of SE. RESULTS AND DISCUSSION: We demonstrated time-dependent significant (p<0.05) differences between the CBF responses in the parietal cortex and the hippocampus during SE. This regional response indicates a preferential distribution of flow to certain regions of the brain and may contribute to the selective vulnerability observed in the hippocampus in humans.