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.