• Che-Chuan Wang, Hsiao-Yue Wee, Chiao-Ya Hu, Chung-Ching Chio, and Jinn-Rung Kuo.
• Department of Neurosurgery, Chi-Mei Medical Center, Tainan, Taiwan; Center for General Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
• World Neurosurg. 2018 Apr 1; 112: e719-e731.

BackgroundThe main aim of this study is to elucidate whether the neuroprotective effect of memantine, a noncompetitive N-methyl-d-aspartate receptor 2B (NR2B) antagonist, affects neuronal nitrosative stress, apoptosis, and NR2B expression and improves functional outcomes.MethodsImmediately after the onset of fluid percussion traumatic brain injury (TBI), anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + memantine groups. TBI rats were treated with a memantine intraperitoneal injection dose of 20 mg/kg intraperitoneally and then 1 mg/kg every 12 hours intraperitoneally for 6 doses. The motor function, proprioception, infarction volume, and neuronal apoptosis were then measured. Immunofluorescence was used to evaluate astrogliosis, microgliosis, nitrosative stress, and NR2A and NR2B expression in cortical cells. All the parameters were assessed 72 hours after TBI.ResultsCompared with the sham-operated controls, the TBI-induced motor and proprioception deficits, and increased infraction volume after TBI were significantly attenuated by memantine therapy. The TBI-induced neuronal apoptosis, astrogliosis, and microgliosis, the numbers of neuronal NO synthase and 3-nitro-l-tyrosine expression in neurons, and inducible NO synthase expression in microglia and astrocyte cells in the ischemic cortex after TBI were significantly improved by memantine therapy. Simultaneously, without affecting the NR2A expression in neuronal cells, the NR2B expression significantly decreased after memantine therapy, as evaluated by an immunofluorescence stain.ConclusionsIntraperitoneal injection of memantine in the acute stage may ameliorate TBI in rats by affecting NR2B expression and decreasing neuronal apoptosis and nitrosative stress in the injured cortex. These effects might represent 1 mechanism by which functional recovery occurred.Copyright © 2018 Elsevier Inc. All rights reserved.

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