Postischemic administration of idazoxan, an alpha-2 adrenergic receptor antagonist, decreases neuronal damage in the rat brain.
The effect of an alpha-2 receptor antagonist, idazoxan, on ischemic neuronal damage in the hippocampus and neocortex was studied in rats following 10 min of forebrain ischemia. Idazoxan was given 0.1 mg/kg i.v. immediately after recirculation, followed by 48 h of continuous infusion at a rate of 10 micrograms/kg/min. A histopathological examination of the CA1 region of the dorsal hippocampus and neocortex from each hemisphere was made on paraffin-embedded sections following 7 days of survival. In ischemic animals receiving an infusion of saline, 71% of the neurons in the hippocampal CA1 region were degenerated. In contrast, in the idazoxan-treated animals only 31% of the neurons were irreversibly damaged (p less than 0.01). We conclude that postischemic administration of the alpha-2 antagonist idazoxan protects neurons against damage following cerebral ischemia. Rapid postischemic administration of alpha-2 adrenergic receptor antagonists could be an effective treatment after stroke and cardiac arrest.
Gustafson
I
I
Laboratory for Experimental Brain Research, University of Lund, Sweden.
Miyauchi
Y
Y
Wieloch
T W
TW
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy* / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D004146:Dioxanes / Q000627:therapeutic use*; D004147:Dioxins / Q000627:therapeutic use*; D019329:Idazoxan; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D019329:Idazoxan