A comparison of protective effects between l-histidine and hypothermia against ischemia-induced neuronal damage in gerbil hippocampus

An increase in the histamine concentration in the brain has been demonstrated to provide protective effects against ischemia/reperfusion brain injury. Since hypothermia and barbiturates are also regarded to protect ischemic brains, effects of postischemic treatments were compared in gerbils between mild hypothermia and intraperitoneal administration of l-histidine, a precursor of histamine. Furthermore, effects of thioperamide, a histamine H3 receptor antagonist, were evaluated in histidine-treated gerbils after 60 days. Transient forebrain ischemia for 4 min at 37 °C provoked severe neuronal damage in the hippocampal CA1 pyramidal cells after 7 days. Postischemic hypothermia (33 °C) for 3 h under pentobarbital anesthesia alleviated neuronal death, and the number of preserved neurons was 77 ± 56/mm (mean ± S.D., n = 14). The effect of l-histidine injected three times, immediately, 6 h, and 24 h after reperfusion (1000 mg/kg, i.p., each), was more prominent than that of hypothermia, and the number of preserved neurons was 142 ± 55/mm (n = 14). When the histologic outcome was evaluated after 60 days, most neurons were damaged in both the hypothermic and histidine groups. The improvement of the histologic outcome was observed even after 60 days in animals injected with thioperamide, immediately and 6 h after reperfusion (5 mg/kg, s.c., each), with three injections of l-histidine. The number of preserved neurons was 133 ± 88/mm (n = 10), while that in the hypothermic group was 7 ± 15 (n = 10). Activation of the central histaminergic system provides beneficial effects against cerebral ischemia.