Local blood flow and glucose consumption in the rat brain during sustained bicuculline-induced seizures

The present study addresses the problem of whether brain structures which have been shown to develop neuronal cell damage in recurrent or prolonged epileptic seizures have higher metabolic rates and/or less pronounced increases in blood flow rates than others during sustained seizures. To that end, local cerebral blood flow (CBF) and glucose utilization (CMRgl) were measured autoradiographically in ventilated rats, in which seizures of 20, 60, or 120 min duration were induced by i.v. bicuculline. After 20 and 60 min of seizure activity, local CBF increased 2- to 4-fold in most of the 21 structures analysed. However, there was a marked heterogeneity with CBF values varying between 150% (caudoputamen) and 500% (globus pallidus) of control. After 120 min, CBF in several structures, notably cortical and limbic regions, fell in spite of unchanged blood pressure and continued seizure activity. Changes in local CMRgl were equally heterogenous, and correlated poorly with blood flow rates. Some structures (the cerebral cortices and 3 limbic areas) showed a sustained 2-4 fold increase in CMRgl. In these, metabolic rate and blood flow were initially matched but CBF subsequently fell to yield a pattern of relative hypoperfusion. Other structures showed no, or only moderate, increases in CMRgl. In spite of this, CBF increased markedly to yield a pattern of relative hyperemia. It is concluded that bicuculline-induced seizures represent a condition in which structures, observed to be prone to develop cell damage, show grossly enhanced metabolic rate and develop relative underperfusion. Furthermore, the results suggest that structures with a large increase of the metabolic rate during seizures, develop a striking mismatch between local metabolic rate and blood flow.