Dexamethasone reduces energy utilization in ischemic gerbil brain.
Glucocorticoids have been reported to aggravate ischemic neuronal damage. Because energy failure is a crucial factor in the development of ischemic neuronal injury, the effects of dexamethasone on histologic outcome and energy metabolism were investigated in gerbil brain. Dexamethasone (3 microg, i.c.v.) was administered 1 h prior to ischemia, and its effect on delayed neuronal death caused by 2 min of bilateral common carotid artery occlusion was observed in hippocampal CA1 pyramidal neurons. The brain concentration of ATP after various durations of decapitation ischemia was determined, and the effect of dexamethasone (3 microg, i.c.v.) was examined. Na+,K+-activated adenosine triphosphatase (Na+,K+-ATPase) activity was evaluated after the administration of the agent. Forebrain ischemia for 2 min produced neuronal damage in animals pretreated with dexamethasone, although neuronal damage was not 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 treatment (3 microg, i.c.v.), whereas the activity at pH 7.4 was not influenced by the agent. The results show that a contributing factor to the aggravation of ischemic neuronal damage may be a disturbance in Na+,K+-ATPase despite adequate levels of ATP.
Adachi
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Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen, Ehime 791-0295, Japan. nadachi@m.ehime-u.ac.jp
Namba
C
C
Nagaro
T
T
Arai
T
T
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005849:Gerbillinae; D005938:Glucocorticoids / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007276:Injections, Intraventricular; D008297:Male; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism
D005938:Glucocorticoids; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase