The effect and possible mechanism of combined rehabilitation therapy with cortical electrical stimulation on somatic motor function for cerebral ischemia rats

Abstract

Objective To investigate the effect of combined rehabilitation therapy with cortical electrical stimulation on somatic motor function in rats with cerebral ischemia, and to explore its possible mechanism. Methods Sixty adult male SD rats were randomly divided into sham surgery group, cerebral ischemia group, cerebral ischemia+ simple exercise therapy (treadmill training) group, cerebral ischemia+ exercise (treadmill training)+ cortical electrical stimulation group, with 15 rats in each group. The middle cerebral artery occlusion (MCAO) was performed and only the successful models were selected as experimental objects. Stimulation electrodes were implanted outside the corresponding cortical area of the affected limbs. Electrical stimulation began on the 3rd day after operation, and the treatment lasted until the 13th day. On the 14th day, Bederson score and fatigue rotating rod test were performed. Immunohistochemical staining or Western Blot was used to detect the expression of CK2α and CaMK Ⅱ in ischemic brain tissue, and to study the possible mechanism of combined rehabilitation therapy with cortical electrical stimulation. Results The survival rate of rats in combined rehabilitation therapy with cortical electrical stimulation was improved, and the Bederson score and fatigue rod rotation time was (0.38±0.15), (155.37±42.44)s respectively, better than those in cerebral ischemia group (t=7.58, 8.95; all P<0.01), and also better than those in exercise only group (t=3.80, 5.58; all P<0.05). Immunohistochemical staining showed that the positive ratios of CK2α and CaMK II in cerebral ischemia group were significantly lower than those in sham group (t=15.99, 12.39; all P<0.01). The positive ratios of CK2α and CaMK Ⅱ in cortical electrical stimulation combined rehabilitation group were (24.75±4.55)% and (33.48±3.23)% respectively, which were significantly higher than those in cerebral ischemia group (t=6.05, 7.99; all P<0.01), and even higher than those in exercise only group (16.40±2.59)%, (22.53±6.44)% (t=4.52, 4.62; all P<0.05). Western Blot results showed that the expression of CK2α and CaMK Ⅱ in cerebral ischemia group decreased significantly to (0.31±0.12), (0.39±0.12) fold of sham group respectively, and those in combined rehabilitation therapy with cortical electrical stimulation increased obviously, which were (0.81±0.08), (0.76±0.19) fold of sham group, with significant differences compared with cerebral ischemia group (t=10.68, 4.73; all P<0.05). Conclusion Combined rehabilitation therapy with cortical electrical stimulation can significantly promote motor function recovery in rats with cerebral ischemia, and which may be related to up-regulation of CK2α and CaMK Ⅱ expression in motor cortex. Key words: Brain ischemia; Cortical electrical stimulation; Combined rehabilitation; Casein Kinase Ⅱ; Calcium/calmodulin-dependent protein kinase-Ⅱ