Sympathetically mediated hypermetabolic response to cerebral ischemia in the rat

Cerebral ischemia, induced in rats by occlusion of the middle cerebral artery resulted in infarcts affecting the basal ganglia and adjacent frontoparietal cortex. Resting oxygen consumption was similar for sham-operated and ischaemic rats immediately after surgery but was elevated in the latter group (peak value 18-21% above controls) 5-6 h post occlusion. By 24 h, these values had returned to control levels. The increase in VO2 was inhibited by injection of the beta-adrenergic antagonist propranolol but was unaffected by injection of the cyclooxygenase inhibitor ibuprofen. The thermogenic activity of brown adipose tissue was assessed from in vitro binding of guanosine diphosphate to mitochondria isolated from intact and surgically denervated lobes of sham-operated and ischemic rats, 6 h after surgery. Brown adipose tissue specific guanosine diphosphate (GDP) binding was elevated by 86% in intact tissue from ischemic compared with sham-operated rats but was identical in denervated tissue from the two groups. Brown adipose tissue activity correlated with resting oxygen consumption in the ischemic group (r = 0.85, p less than 0.01) but not in controls (r = -0.35, NS). Thus occlusion of the middle cerebral artery in the rat may provide a representative model for both stroke and head injury in man. It is associated with a transient increase in metabolic rate and by sympathetically mediated activation of brown adipose tissue in the rat.