Alleviation of ischemic neuronal damage by postischemic loading with histidine in the rat striatum.
Inflammatory reactions play an important role in ischemia-reperfusion injury in the brain. Since histamine H(2) action suppresses inflammatory reactions, effects of postischemic loading with histidine, a precursor of histamine, were examined. Focal cerebral ischemia for 15 min was provoked by transient occlusion of the right middle cerebral artery in rats, and delayed neuronal death were evaluated in striatal neurons after 7 days. Histidine was administered four times, immediately, 6, 24, and 48 h after reperfusion of blood flow (1000 mg/kg, i.p., each time). To examine the role of histaminergic action on changes in histologic outcome, effects of mepyramine (3 nmol, i.c.v.), an H(1) antagonist, and ranitidine (30 nmol, i.c.v.), an H(2) antagonist, were evaluated in histidine-treated rats. Transient ischemia for 15 min provoked severe neuronal damage in the saline-injected control group, and the number of striatal neurons decreased to 21% of that on the contralateral side. Administration of histidine alleviated ischemic neuronal damage, and the number of preserved neurons was 76% of that on the contralateral side. Simultaneous administration of mepyramine with histidine did not affect the histologic outcome. However, administration of ranitidine abolished the alleviation by histidine. These findings indicate that the elevation of histamine H(2) receptor stimulation by massive administration of histidine suppresses reperfusion injury in the brain.
Adachi
Naoto
N
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. nadachi@m.ehime-u.ac.jp
Liu
Keyue
K
Arai
Tatsuru
T
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004347:Drug Interactions; D007839:Functional Laterality; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006639:Histidine / Q000008:administration & dosage* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011738:Pyrilamine / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion / Q000379:methods; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D006639:Histidine; D011899:Ranitidine; D011738:Pyrilamine