Effect of CB1 receptor on spatial learning and memory in mice with traumatic brain injury

Ma Fuxing; Zhou Zhongqing; Xue Shilei; Xie Zhanbing; Kong Chuanxiang

doi:10.3969/j.issn.1009-6574.2019.07.006

Abstract：Objectives? To investigate the role of Cannabinoid receptor 1 (CB1) on the spatial learning and memory function in mice with traumatic brain injury (TBI). Methods? The concussive head trauma device was used to induce experimental TBI models. Mice were divided into control group, TBI+Vehicle group and TBI+AM281 group. The control group received sham surgery and AM281 solvent. The TBI+Vehicle group received AM281 solvent after injury treatment, and the TBI+AM281 group received CB1 receptor antagonist AM281 after injury treatment. Western blot was used to detect the expression of CB1 receptor and NR2B protein. The mass and volume of cerebral infarction area in mice were detected by Evansland staining. The spatial learning and memory ability of mice were tested by water maze experiment. TUNEL staining was used to label apoptotic neurons and detect the tune level of neurons in the hippocampus. Results? After TBI, the expression level of CB1 in the TBI+Vehicle group at day 1 and day 3 increased significantly compared with that in the control group. In the TBI+Vehicle group, there were significant differences in infarct area mass and infarct volume compared with the TBI+AM281 group. In the TBI+Vehicle group, compared with the control group, the time to find the platform prolonged significantly, and the percentage of stay time in the quadrant of the platform reduced significantly. In the TBI+AM281 group, compared with the solvent group, the time to find the platform reduced significantly, and the time to stay in the quadrant of the platform increased significantly. In TUNEL staining, the administration of AM281 after TBI significantly reduced the apoptosis percentage of neurons and reversed the decreased NR2B expression level caused by TBI. Conclusions? CB1 receptor was involved in the process of impaired spatial learning and memory ability in mice after TBI. Administration of CB1 receptor antagonist can reverse this injury, which may be mediated by NMDA receptor subunit NR2B.