Yi Nan-Xing, Zhou Long-Yun, Wang Xiao-Yun, Song Yong-Jia, Han Hai-Hui, Zhang Tian-Song, Wang Yong-Jun, Shi Qi, Xu Hao, Liang Qian-Qian, Zhang Ting
Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine; Institute of Spine, Shanghai University of Traditional Chinese Medicine; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, China.
Institute of Spine, Shanghai University of Traditional Chinese Medicine; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education; School of Rehabilitation Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Neural Regen Res. 2019 Nov;14(11):1919-1931. doi: 10.4103/1673-5374.259619.
To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.
Key terms were "stroke", "brain diseases", "brain injuries", "brain hemorrhage, traumatic", "acute brain injury", "dizocilpine maleate", "dizocilpine", "MK-801", "MK801", "rat", "rats", "rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform (VJIP) and SinoMed databases were searched from their inception dates to March 2018.
Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.
The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.
A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P < 0.00001) and degree of cerebral edema (5 studies, n = 75, MD = -1.21, 95% CI: -1.50 to -0.91; P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test (2 studies, n = 60, MD = -10.88, 95% CI: -20.75 to -1.00; P = 0.03) and neurological function 24 hours after brain injury (11 studies, n = 335, MD = -1.04, 95% CI: -1.47 to -0.60; P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P = 0.004). Further network analysis showed that 0-1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.
MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.
评估MK-801在大鼠急性脑损伤模型中的疗效、安全性及其对损伤体积的影响。
检索词为“中风”“脑部疾病”“脑损伤”“脑出血，创伤性”“急性脑损伤”“马来酸二氮卓西平”“二氮卓西平”“MK-801”“MK801”“大鼠”“鼠科动物”。检索了PubMed、Cochrane图书馆、EMBASE、中国知网、万方数据库、维普资讯中文科技期刊数据库和中国生物医学文献数据库，检索时间从建库至2018年3月。
纳入报告MK-801在实验性急性脑损伤中作用的研究。两名研究者独立进行文献筛选、数据提取和方法学质量评估。
主要指标包括损伤体积和脑水肿。次要指标包括脑损伤24小时后采用贝德森神经功能评分系统和水迷宫试验进行的行为评估。
系统评价共纳入52项研究，2530个样本。其中17项研究方法学质量高。总体而言，与对照组相比，MK-801组的损伤体积（34项研究，n = 966，MD = -58.31，95%CI：-66.55至-50.07；P < 0.00001）和脑水肿程度（5项研究，n = 75，MD = -1.21，95%CI：-1.50至-0.91；P < 0.00001）显著降低。MK-801改善了水迷宫试验评估的空间认知（2项研究，n = 60，MD = -10.88，95%CI：-20.75至-1.00；P = 0.03）以及脑损伤24小时后的神经功能（11项研究，n = 335，MD = -1.04，95%CI：-1.47至-0.60；P < 0.00001）。亚组分析表明损伤体积的减小与各种损伤模型相关（34项研究，n = 966，MD = -58.31，95%CI：-66.55至-50.07；P = 0.004）。进一步的网状分析表明，0 - 1mg/kg MK-801可能是大脑中动脉闭塞动物模型治疗的最佳剂量。
MK-801可有效降低实验性急性脑损伤大鼠模型的脑损伤体积和脑水肿程度，具有良好的神经保护作用。此外，MK-801安全性良好，其作用机制明确。因此，MK-801可能适用于未来的临床试验和应用。
