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| kappa opioid receptor agonist protects cognitive function in mice with mild craniocerebral blast injury and its possible mechanism |
| Gao Lei, Dai Jing, Liu Ying, Liu Yun-en, Jin Hong-xu |
| Department of Emergency Medicine, General Hospital of Shen-Yang Military Region, Shenyang 110840, China |
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Abstract Objective To investigate the changes of cognitive function in mice after mild blast injury and the protective effect of kappa opioid receptor specific agonist U50488 on it and its possible mechanism. Methods The male Kunming mice were randomly divided into control group (group S), blast injury model group (group b-TBI), and U50488 intervention group (b-TBI+U50488 group), 20 rats in each group; each group was further divided into 1 d, 3 d, 7 d, and water maze group, four subgroups after injury, 5 rats in each group. The homemade explosive injury automatic device was used to make explosive injury model in mice. The mice in KORS group were given U50488U 10 mg/kg of U50488 15 min before the shock. The mice in the sham group and b-TBI group were given only the same amount of normal saline before injury. Western blot was used to detect the high mobility protein family (HMGB-1), interleukin-1 (IL-1) and cholinergic anti-inflammatory pathway protein in the brain tissue of mice in each group. The cognitive function was evaluated by using water maze escape latency and mNSS score. Results Compared with the blank control group, the mNSS score of the mice in the b-TBI group was higher than that in the control group; Water maze escape assay showed that the latency was longer (P<0.05); and the expression of IL-1 and HMGB-1 in central nervous system increased significantly (P<0.05). Compared with b-TBI group, the mNSS score of mice in U50488 intervention group decreased significantly, and the escape latency of water labyrinth decreased significantly (P<0.05), but the expression of α7nAChR associated with cholinergic anti-inflammatory pathway was increased (P<0.05). Conclusion Mild blast brain injury can lead to cognitive dysfunction, and is closely related to the occurrence of brain inflammation. The activation of Kappa opioid receptor can protect the cognitive function of mice after blast injury. The mechanism of action may be related to the activation of cholinergic anti-inflammatory pathways and reduce the central nervous system inflammatory response.
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Corresponding Authors:
Jin Hong-xu, E-mail：hongxuj@126.com
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