Suppression of inflammatory cell recruitment by histamine receptor stimulation in ischemic rat brains.

Inflammation is a crucial factor in the development of ischemia-induced brain injury. Since facilitation of central histaminergic activity ameliorates reperfusion injury, effects of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H3 receptor antagonist, on inflammatory cell infiltration were evaluated in a rat model of transient occlusion of the middle cerebral artery. After reperfusion for 12, 24, or 72 h following 2 h of occlusion, brain slices were immunohistochemically stained with antibodies against myeloperoxidase and CD68, which were markers of polymorphonuclear leukocytes and macrophages/microglia, respectively. After reperfusion for 12-24 h, the number of neutrophils on the ischemic side increased markedly, whereas the increase was not observed on the contralateral side. Administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the number of neutrophils to 52%. Simultaneous administration of thioperamide (5 mg/kg, s.c.) further decreased the number of neutrophils to 32%. Likewise, the ischemia induced increase in the number of CD68-positive cells after 24 h was suppressed by L-histidine injections. The L-histidine administration decreased the number of CD4+ T lymphocytes on both ischemic and contralateral sides after 12 h, and concurrent administration of thioperamide prolonged the effect. Although administration of mepyramine (3 nmol, i.c.v.) did not affect suppression of leukocyte infiltration, ranitidine tended to reverse the effect of L-histidine. These data suggest that enhancement of central histaminergic activity suppresses inflammatory cell recruitment after ischemic events through histamine H2 receptors, which may be a mechanism underlying the protective effect of L-histidine.
AuthorsNorihito Hiraga, Naoto Adachi, Keyue Liu, Takumi Nagaro, Tatsuru Arai
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 557 Issue 2-3 Pg. 236-44 (Feb 28 2007) ISSN: 0014-2999 [Print] Netherlands
PMID17169356 (Publication Type: Journal Article)
Chemical References
  • Antigens, CD
  • Drug Combinations
  • Histamine H1 Antagonists
  • Histamine H2 Antagonists
  • Piperidines
  • Receptors, Histamine
  • thioperamide
  • Histidine
  • Ranitidine
  • Peroxidase
  • Pyrilamine
  • Animals
  • Antigens, CD (metabolism)
  • Brain Ischemia (complications, drug therapy)
  • CD4-Positive T-Lymphocytes (drug effects)
  • Cell Count
  • Drug Combinations
  • Histamine H1 Antagonists (pharmacology)
  • Histamine H2 Antagonists (pharmacology)
  • Histidine (pharmacology, therapeutic use)
  • Immunohistochemistry
  • Infarction, Middle Cerebral Artery (complications, drug therapy)
  • Male
  • Neutrophils (drug effects)
  • Peroxidase (metabolism)
  • Piperidines (pharmacology)
  • Pyrilamine (pharmacology)
  • Random Allocation
  • Ranitidine (pharmacology)
  • Rats
  • Rats, Wistar
  • Receptors, Histamine (metabolism)
  • Reperfusion (methods)
  • Time Factors

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