Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (11): 1919-1931.doi: 10.4103/1673-5374.259619

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MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis

Nan-Xing Yi 1, 2, 3 , Long-Yun Zhou 2, 3, 4 , Xiao-Yun Wang 1 , Yong-Jia Song 1, 2, 3 , Hai-Hui Han 2, 5 , Tian-Song Zhang 6 , Yong-Jun Wang 2, 3 , Qi Shi 1, 2, 3, 5 , Hao Xu 1, 2, 3 , Qian-Qian Liang 1, 2, 3 , Ting Zhang 1, 2   

  1. 1 Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2 Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    3 Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, China
    4 School of Rehabilitation Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    5 Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
    6 Jing’an District Center Hospital, Fudan University, Shanghai, China
  • Online:2019-11-15 Published:2019-11-15
  • Contact: Hao Xu, PhD, HOXU@163.com; Qian-Qian Liang, PhD, liangqianqiantcm@126.com; Ting Zhang, PhD, ztingdd@hotmail.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81822050, 81873321, 81673990, 81330085 , 81730107; the Shanghai Municipal Health and Family Planning Commission TCM Research Project of China, No. 2018JP014 ; the Three-Year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals of China, No. 16CR1017A; the Shanghai Traditional Chinese Medicine Chronic Disease [Malignant Tumor, Bone Degenerative Disease] Clinical Medical Center of China, No. 2017ZZ01010; the National Ministry of Education Innovation Team of China, No. IRT1270; the Innovation Team of Key Fields of the Ministry of Science and Technology of China, No. 2015RA4002.  

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Abstract:

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.
DATA SOURCES: 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.
DATA SELECTION: Studies were selected if they reported the effects of MK-801 in  xperimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.
OUTCOME MEASURES: 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.
RESULTS:  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.
CONCLUSION: 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.

Key words: nerve regeneration, acute brain injury, neurological function, spatial cognition, water maze test, lesion volume, brain edema, rat, systematic review, meta-analysis, neural regeneration