Memantine Alleviates Brain Injury and Neurobehavioral Deficits after Experimental Subarachnoid Hemorrhage

Chih Yuan Huang, Liang Chao Wang, Hao Kuang Wang, Chia Hsin Pan, Ya Yun Cheng, Yan Shen Shan, Chung Ching Chio, Kuen Jer Tsai

研究成果: Article

17 引文 斯高帕斯(Scopus)

摘要

Subarachnoid hemorrhage (SAH) causes brain injury via glutamate excitotoxicity, which leads to an excessive Ca2+ influx and this starts an apoptotic cascade. Memantine has been proven to reduce brain injury in several types of brain insults. This study investigated the neuro-protective potential of memantine after SAH and explored the underlying mechanisms. An endovascular perforation rat model of SAH was used and Sprague–Dawley rats were randomized into sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the neuro-behavioral functions, blood–brain barrier (BBB) permeability and neuronal cell preservation. The mechanisms of action of memantine, with its N-methyl-d-aspartate (NMDA) antagonistic characteristics on nitric oxide synthase (NOS) expression and peroxynitrite formation, were also investigated. The apoptotic cascade after SAH was suppressed by memantine. Neuronal NOS (nNOS) expression, peroxynitrite formation, and subsequent oxidative/nitrosative stress were also reduced. Memantine effectively preserved BBB integrity, rescued neuronal injury, and improved neurological outcome in experimental SAH. Memantine has neuro-protective potential in experimental SAH and may help combat SAH-induced brain damage in the future.

原文English
頁(從 - 到)1038-1052
頁數15
期刊Molecular Neurobiology
51
發行號3
DOIs
出版狀態Published - 2015 六月 1

    指紋

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

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