TY - JOUR
T1 - Memantine Alleviates Brain Injury and Neurobehavioral Deficits after Experimental Subarachnoid Hemorrhage
AU - Huang, Chih Yuan
AU - Wang, Liang Chao
AU - Wang, Hao Kuang
AU - Pan, Chia Hsin
AU - Cheng, Ya Yun
AU - Shan, Yan Shen
AU - Chio, Chung Ching
AU - Tsai, Kuen Jer
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84939877500&partnerID=8YFLogxK
U2 - 10.1007/s12035-014-8767-9
DO - 10.1007/s12035-014-8767-9
M3 - Article
C2 - 24952609
AN - SCOPUS:84939877500
VL - 51
SP - 1038
EP - 1052
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
IS - 3
ER -