Effect of Hypothermia by JZL-184 on Muscle Strength and Sensory-Motor Dysfunction in Permanent Middle Cerebral Artery Ischemia Model in Male Mice

Abstract

Introduction: Currently, there is no effective and comprehensive treatment for ischemic stroke. There is strong clinical evidence for the benefits of hypothermia in neuroprotection. Therefore, the present study aimed to determine the effect of mild non-invasive hypothermia by JZL-184 on behavioral improvement in stroke rats.

Methods: This study was performed on 5 groups of male mice weighing 25-30 g. The groups were as follows: 1- Healthy group 2- Control group (Stroke) 3- Stroke + DMSO solvent 4- Stroke + Aspirin (40mg /kg) 5- Stroke + JZL-184 (16mg / kg) (n = 8 per group). The drugs were injected intraperitoneally immediately after the stroke. At the times before (time zero) and at 5, 24 and 48 h after stroke induction, body temperature, behavioral testing, including muscle strength and sensory-motor dysfunction were measured. Data were analyzed by SPSS version 18 software and Two-way ANOVA test (P ≤ 0.05).

Results: JZL-184 decreased body temperature at 5, 24 and 48 hours compared to intact and control groups (p <0.001). Injection JZL-184 and Aspirin improved muscle strength and sensory-motor function (p <0.001) compared to the control group. Aspirin also improved behavioral tests compared to the control group (p <0.01), but did not show any effect on the body temperature compared to the intact group at time 48. Only in JZL-184 group, the behavioral tests score was similar to the intact group at the 48 h after stroke.

Conclusion: JZL-184 may have been able to improve neuronal function by hypothermia induced by the agonist effects of cannabinoid receptor 1 (CB1), thereby improving muscle strength and sensory-motor function after cerebral ischemia.