Dexamethasone reduces energy utilization in ischemic gerbil brain

Glucocorticoids have been reported to aggravate ischemic neuronal damage. B ecause energy failure is a crucial factor in the development of ischemic ne uronal injury, the effects of dexamethasone on histologic outcome and energ y metabolism were investigated in gerbil brain. Dexamethasone (3 mug, i.c.v .) was administered 1 h prior to ischemia. and its effect on delayed neuron al death caused by 2 min of bilateral common carotid artery occlusion was o bserved in hippocampal CA1 pyramidal neurons. The brain concentration of AT P after various durations of decapitation ischemia was determined, and the effect of dexamethasone (3 mug, i.c.v.) was examined. Na+,K+-activated aden osine triphosphatase (Na+,K+-ATPase) activity was evaluated after the admin istration of the agent. Forebrain ischemia for 2 min produced neuronal dama ge in animals pretreated with dexamethasone, although neuronal damage was n ot observed in vehicle-injected animals. Decapitation ischemia for 0.5 and 1 min reduced the brain ATP concentration to 44% and 15% of the basal level , respectively. Dexamethasone attenuated the ischemia-induced reduction in ATP, and the values were 58% and 25% of the basal level, respectively. Na+, K+-ATPase activity at pH 6.7 was suppressed to 47% by dexamethasone treatme nt (3 mug, i.c.v.), whereas the activity at pH 7.4 was not influenced by th e agent. The results show that a contributing factor to the aggravation of ischemic neuronal damage may be a disturbance in Na+,K+-ATPase despite adeq uate levels of ATP. (C) 2001 Elsevier Science B.V. All rights reserved.