AGGRAVATION OF ISCHEMIC NEURONAL DAMAGE IN THE RAT HIPPOCAMPUS BY IMPAIRMENT OF HISTAMINERGIC NEUROTRANSMISSION

Delayed damage to hippocampal CA1 pyramidal cells was observed in rats subjected to cerebral ischemia caused by 10 min of 4-vessel occlusion. Animals pretreated with alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, showed significantly more necrotic cells than did control animals. Mepyramine (H-1-antagonist) and (R)alpha-methylhistamine (H-3-agonist), but not zolantidine (H-2-antagonist), significantly aggravated the delayed neuronal death. These results suggest that histaminergic neurons have a protective role, probably via H-1-receptors, in the development of delayed neuronal death caused by cerebral ischemia.