CEREBRAL BLOOD FLOW AND METABOLIC RATE EARLY AND LATE IN PROLONGED EPILEPTIC SEIZURES INDUCED IN RATS BY BICUCULLINE

Abstract

Cerebral blood flow (CBF) and cerebral metablic rate for oxygen (CMRO2) have been studied during sustained epileptic seizures induced by bicuculline (1-2 mg/kg, i.v.) in paralysed Wistar rats, artificially ventilated with nitrous oxide/oxygen. CBF was determined by venous outflow collection, and by 133Xe desaturation, using sagittal sinus blood (for cerebral cortical flow) or retroglenoid venous blood (for 'whole brain' flow). The procedure employed ensured that arterial oxygenation remained normal and blood glucose concentration was normal or high throughout the seizure. Arterial hypotension was prevented by the infusion of donor blood. CBF increased concurrently with seizure onset, reaching a maximum nine times higher than control value after 15-60 s. This was due to a marked rise in mean arterial pressure (to greater than 180 torr) and a dramatic fall in cerebrovascular resistance to less than 15 per cent of control). Subsequently, with decreasing blood pressure, CBF slowly diminished, being more than four times higher than control at 20 min, and slightly less than three times higher than control at two hours. The different procedures for measuring CBF gave closely similar results. A threefold increase relative to control CMRO2 (7-6 ml/100 g-1/min-1 for 'whole brain,' and 10-2 ml/100 g-1/min-1 for cerebral cortex) was measured after 1-20 min of seizure activity (utilizing either the venous outflow or the 133Xe desaturation procedure for CBF determination). After two hours of seizure activity CMR02 was still more than twice as high as the control. This high metabolic rate during sustained seizure activity will increase the susceptibility of the brain to 'ischaemic' damage during prolonged seizures in man in which an additional metabolic stress may be imposed by cerebral hypoxia, arterial hypotension, hyperpyrexia or hypoglycaemia.