Effect of a specific inhibitor of histamine synthesis enzyme (FMH) on the ischemic neuronal death of gerbil hippocampus

• Published in: Japanese Journal of Pharmacology 1995, Vol.67 (suppl.1), p.150-150
• Main Authors: Koreaki Sugimoto, Kazuhiko Yanai, Eiko Sakurai, Yasuto Itoyama, Takehiko Watanabe
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Histamine is a putative neurotransmitter or neuromodulator in mammalian brain, and neuronal histamine has many physiological functions such as in the circadian rhythm, feeding behavior, motion sickness, and suppression of convulsion. But there are few reports on the relationship between brain histamine and ischemia. So we studied the effect of α-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase (HDC), on ischemic neuronal death of gerbil hippocampus. 「METHODS」 l)Histaminergic neurons of the hypothalamus of gerbil were stained by immunohistochemistry with anti-HDC antibody. 2)Histamine contents of the cortex, diencephalon (hypothalamus plus thalamus), and hippocampus of gerbil 2 h after subcutaneous injection of FMH (100 or 200 mg/kg body weight) were measured by fluorometric-HPLC system. 3)Two hours after injection of FMH, brain ischemia was induced by transient 2 or 3 min occlusion of bilateral carotid arteries. Seven days after the transient ischemia, the brains were removed and embedded in paraffin with receiving conventional fixation. Ischemia-induced hippocampal cell damage was estimated by light microscopic observation of brain sections (5 μm) with cresyl violet - staining. 「RESULTS」 1)It was shown that histaminergic neurons were present in gerbil brain. 2)Histamine contents of the cortex, diencephalon, and hippocampus were decreased to approximately 20, 47, and 56 %, respectively, of saline treated group by FMH administration. 3)FMH administration enhanced ischemic neuronal death of hippocampal CA1 region by 2 min ischemia, and of CA2 region by 3 min ischemia. 「CONCLUSION」 These results suggest that histamine depletion aggravates ischemic neuronal death of the hippocampus.