Reduction in brain infarction by augmentation of central histaminergic activity in rats

Inflammation is a factor in the aggravation of reperfusion injury after cerebral ischemia. Since histamine H 2 receptor stimulation suppresses inflammatory reactions, effects of the central histaminergic activation on brain infarction were examined in rats. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery, and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride stain after 24 h. Effects of postischemic administration of thioperamide, an H 3 antagonist, and metoprine, an inhibitor of histamine- N-methyltransferase, were evaluated in rats treated with l-histidine, a precursor of histamine. Furthermore, effects of these agents on changes in the striatal histamine level were examined by a microdialysis procedure. Focal ischemia provoked marked damage in rats treated with l-histidine (1000 mg/kg) alone. Administration of l-histidine (1000 mg/kg) with either thioperamide (5 mg/kg) or metoprine (10 mg/kg) alleviated brain infarction. The size of brain infarction was 27% and 10% of that in animals treated solely with l-histidine, respectively. The combination treatment with thioperamide and metoprine decreased the size of brain infarction in rats given l-histidine (500 mg/kg), although protective effects were not clear without l-histidine. A marked increase in the histamine concentration was observed in the histidine plus metoprine group, the value being 363% of that in the saline-injected group after 2–3 h. The histamine concentrations in the histidine group and histidine plus thioperamide group were 188% and 248%, respectively. These findings indicate that facilitation of central histaminergic activity reduced the brain infarction.