title: Memantine alleviates brain injury and neurobehavioral deficits after experimental subarachnoid hemorrhage.
abstract: Subarachnoid hemorrhage (SAH) causes brain injury via glutamate excitotoxicity, which leads to an excessive Ca(2+) 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.
authors: Institute of Clinical Medicine, National Cheng Kung University, Tainan, 704, Taiwan.
authors: Chih-Yuan
authors: CY
authors: Huang
authors: Liang-Chao
authors: LC
authors: Wang
authors: Hao-Kuang
authors: HK
authors: Wang
authors: Chia-Hsin
authors: CH
authors: Pan
authors: Ya-Yun
authors: YY
authors: Cheng
authors: Yan-Shen
authors: YS
authors: Shan
authors: Chung-Ching
authors: CC
authors: Chio
authors: Kuen-Jer
authors: KJ
authors: Tsai
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use*; D001523:Mental Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D008559:Memantine