Alleviation of ischemic neuronal damage by histamine H2 receptor stimulation in the rat striatum.
Transient ischemia was produced for 15 min by occlusion of the middle cerebral artery in halothane-anesthetized rats, and changes in the extracellular concentrations of neurotransmitter monoamines and amino acids were examined in the striatum. The occlusion produced marked increases in the extracellular concentrations of both dopamine and glutamate in the striatum in the saline-injected control group, the peak values being 148 and 5.2 times those before ischemia, respectively. Preischemic administration of histamine (200 nmol, i.c.v.) suppressed the increase in dopamine and glutamate levels during ischemia, the peak values being 38% and 40% of those in the control group, respectively. Neither the dopamine nor glutamate level was affected by 6-[2-(4-imidazolyl)ethylamino]-N-(trifluoromethylphenyl)heptanecarboxamide (HTMT), an H(1) agonist (100 nmol, i.c.v.). However, dimaprit, an H(2) agonist (100 nmol, i.c.v.) suppressed the peak values to 42% and 32%, respectively. Most neurons were degenerated 7 days after ischemia in control animals. Histologic outcome was alleviated by either histamine or dimaprit treatment, whereas HTMT did not affect the outcome. Although postischemic administration of mepyramine, an H(1) antagonist (5 nmol, i.c.v.), did not affect the histologic alleviation caused by preischemic treatment with histamine, ranitidine, an H(2) antagonist (30 nmol, i.c.v.), partly abolished the improvement caused by histamine. These results suggest that suppression of ischemic release of excitatory neurotransmitters by histamine H(2) action is a contributing factor in alleviation of histologic outcome.
Hamami
Gen
G
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan.
Adachi
Naoto
N
Liu
Keyue
K
Arai
Tatsuru
T
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000378:metabolism*
D011970:Receptors, Histamine H2; D006632:Histamine; D004298:Dopamine