Cerebral ischemia and brain histamine.

Cerebral ischemia induces excess release of glutamate and an increase in the intracellular Ca(2+) concentration in neurons, which provokes enzymatic process leading to irreversible neuronal injury. Histamine plays a role as a neurotransmitter in the mammalian brain, and histamine release from nerve endings is enhanced in ischemia by facilitation of histaminergic activity. Dissimilar to ischemia-induced release of glutamate, histamine release is gradual and long lasting. The enhancement may contribute to neuroprotection against ischemic damage, because suppression of histaminergic activity aggravates the histologic outcome caused by ischemia. Preischemic administration of histamine (i.c.v.) suppresses ischemic release of glutamate and ameliorates neuronal damage, whereas blockade of central histamine H(2) receptors aggravates ischemic injury. These suggest that histamine provides beneficial effects against ischemic damage through histamine H(2) receptors, when administered before induction of ischemia. Postischemic loading with histidine, a precursor of histamine, alleviates both brain infarction and delayed neuronal death. Since the alleviation is abolished by blockade of central histamine H(2) receptors, facilitation of central histamine H(2) action caused by histidine may prevent reperfusion injury after ischemic events. Because the ischemia-induced increase in the glutamate level rapidly resumes after reperfusion of cerebral blood flow, beneficial effects caused by postischemic loading with histidine may be due to other mechanisms besides suppression of excitatory neurotransmitter release. Anti-inflammatory action by histamine H(2) receptor stimulation is a likely mechanism responsible for the improvement.
AuthorsNaoto Adachi
JournalBrain research. Brain research reviews (Brain Res Brain Res Rev) Vol. 50 Issue 2 Pg. 275-86 (Dec 15 2005) Netherlands
PMID16181682 (Publication Type: Journal Article, Review)
Chemical References
  • Neurotransmitter Agents
  • Receptors, Histamine
  • Histidine
  • Histamine
  • Animals
  • Brain Ischemia (drug therapy, metabolism)
  • Histamine (metabolism, therapeutic use)
  • Histidine (therapeutic use)
  • Humans
  • Models, Neurological
  • Neurotransmitter Agents (metabolism)
  • Receptors, Histamine (physiology)

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