Adachi Naoto
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Touon-shi, Ehime 791-0295, Japan.
Brain Res Brain Res Rev. 2005 Dec 15;50(2):275-86. doi: 10.1016/j.brainresrev.2005.08.002. Epub 2005 Sep 21.
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.
脑缺血会导致谷氨酸过量释放以及神经元细胞内钙离子浓度升高，从而引发酶促过程，导致不可逆的神经元损伤。组胺在哺乳动物大脑中作为神经递质发挥作用，缺血时通过促进组胺能活性，神经末梢的组胺释放会增强。与缺血诱导的谷氨酸释放不同，组胺释放是渐进且持久的。这种增强可能有助于对缺血性损伤的神经保护，因为抑制组胺能活性会加重缺血引起的组织学结果。缺血前给予组胺（脑室内注射）可抑制谷氨酸的缺血性释放并减轻神经元损伤，而阻断中枢组胺H2受体则会加重缺血性损伤。这些表明，在缺血诱导前给药时，组胺通过组胺H2受体对缺血性损伤具有有益作用。缺血后给予组胺的前体组氨酸，可减轻脑梗死和延迟性神经元死亡。由于这种减轻作用可被中枢组胺H2受体阻断所消除，组氨酸引起的中枢组胺H2作用的增强可能会预防缺血事件后的再灌注损伤。因为脑血流再灌注后，缺血诱导的谷氨酸水平升高会迅速恢复，缺血后给予组氨酸产生的有益作用可能是由于除抑制兴奋性神经递质释放之外的其他机制。组胺H2受体刺激的抗炎作用可能是导致这种改善的一个机制。
