Activation of the central histaminergic system is involved in hypoxia-induced stroke tolerance in adult mice

Yan Ying Fan, Wei Wei Hu, Hai Bin Dai, Jian Xiang Zhang, Lu Yi Zhang, Ping He, Yao Shen, Hiroshi Ohtsu, Er Qing Wei, Zhong Chen

研究成果: Article査読

48 被引用数 (Scopus)


We hypothesized that activation of the central histaminergic system is required for neuroprotection induced by hypoxic preconditioning. Wild-type (WT) and histidine decarboxylase knockout (HDC-KO) mice were preconditioned by 3 hours of hypoxia (8% O2) and, 48 hours later, subjected to 30 minutes of middle cerebral artery (MCA) occlusion, followed by 24 hours of reperfusion. Hypoxic preconditioning improved neurologic function and decreased infarct volume in WT or HDC-KO mice treated with histamine, but not in HDC-KO or WT mice treated with α-fluoromethylhistidine (α-FMH, an inhibitor of HDC). Laser-Doppler flowmetry analysis showed that hypoxic preconditioning ameliorated cerebral blood flow (CBF) in the periphery of the MCA territory during ischemia in WT mice but not in HDC-KO mice. Histamine decreased in the cortex of WT mice after 2, 3, and 4 hours of hypoxia, and HDC activity increased after 3 hours of hypoxia. Vascular endothelial growth factor (VEGF) mRNA and protein expressions showed a greater increase after hypoxia than those in HDC-KO or α-FMH-treated WT mice. In addition, the VEGF receptor-2 antagonist SU1498 prevented the protective effect of hypoxic preconditioning in infarct volume and reversed increased peripheral CBF in WT mice. Therefore, endogenous histamine is an essential mediator of hypoxic preconditioning. It may function by enhancing hypoxia-induced VEGF expression.

ジャーナルJournal of Cerebral Blood Flow and Metabolism
出版ステータスPublished - 2011 1月

ASJC Scopus subject areas

  • 神経学
  • 臨床神経学
  • 循環器および心血管医学


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