创伤性脑损伤导致谷氨酸释放,过度刺激N-甲基-D-天冬氨酸(NMDA)受体,导致神经毒性和细胞毒性水肿。NMDA受体拮抗剂可通过阻断该途径提供神经保护。本系统综述的目的是评估NMDA受体拮抗剂对啮齿动物模型中创伤性脑损伤引起的脑水肿的疗效。该系统评价遵循Cochrane手册指南,并在PROSPERO(ID:CRD42023440934)中注册了其协议。这里,我们纳入对照啮齿动物动物模型,比较使用NMDA拮抗剂和安慰剂治疗.结果措施包括减少脑水肿,神经行为严重程度量表,和不利影响。搜索策略使用与创伤性脑损伤和NMDA受体拮抗剂相关的医学主题词。采用协同方法进行Meta分析和动物实验研究综述(CAMARADES)检查表和实验动物实验系统评价中心(SYRCLE)工具来衡量纳入研究的质量和偏倚。结果的综合呈现在标准平均差异的荟萃分析中。包括16项研究,主要的药物是艾芬普地尔,MK-801镁,还有HU-211.受试者由Sprague-Dawley或Sabra大鼠组成。分析显示NMDA拮抗剂治疗可显著减轻脑水肿(标准化平均差[SMD]-1.17,95%置信区间[CI]-1.59至-0.74,p<0.01),尽管异质性高(I2=72%)。在接受NMDA拮抗剂的动物中,神经行为严重程度量表也显著改善(平均差异-3.32,95%CI-4.36至-2.28,p<0.01)。与基线相比,损伤后1小时内的给药在减少脑水肿方面表现出适度的增强(SMD-1.23,95%CI-1.69至-0.77,p<0.01)。研究符合动物福利和模型适当性的标准。尽管基线可比性和选择性报告偏差得到了普遍解决,关键偏见,如随机化,分配隐藏,和盲法通常未报告。总的来说,NMDA拮抗剂在治疗创伤性脑损伤中表现出有希望的功效。值得注意的是,我们的系统评价一致表明,包括HU-211和NPS150在内的化合物可显著减轻脑水肿.
Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA
antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation\'s (SYRCLE\'s) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA
antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I2 = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1 h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.