CHANGES IN THE METABOLISM OF HISTAMINE AND MONOAMINES AFTER OCCLUSION OF THE MIDDLE CEREBRAL-ARTERY IN RATS

Changes in the levels of histamine, monoamines, and their metabolites in the cerebral cortex and striatum after occlusion of the middle cerebral artery in rats were examined. The water content of the ipsilateral brain regions gradually increased after occlusion. In the ischemic side, 1 h after occlusion, the cortical norepinephrine and striatal 5-hydroxytryptamine levels significantly decreased, and striatal 3,4-dihydroxyphenylacetic acid and homovanillic acid levels markedly increased. In contrast, the levels of histamine and tele-methylhistamine in either brain region gradually increased and the changes became pronounced and statistically significant 6-12 h after induction of ischemia. The striatal histamine and tele-methylhistamine reached levels three- and twofold higher, respectively, than those of the contralateral side. In rats treated with alpha-fluoromethylhistidine 1 h before induction of ischemia, elevation of histamine and tele-methylhistamine was not observed. The elevated histamine level in the ipsilateral striatum at 9 h after occlusion was further significantly increased by the treatment with metoprine, an inhibitor of histamine-N-methyltransferase. These results suggest that the histaminergic activity in the brain is gradually enhanced by cerebral ischemia.