The effect of continuous epidural electrical stimulation on neuronal proliferation in cerebral ischemic rats

Abstract

Objective: To investigate the effect of electrical stimulation (ES) on the recovery of motor skill and neuronal cell proliferation.

Methods: The male Sprague-Dawley rats were implanted with an epidural electrode over the peri-ischemic area after photothrombotic stroke in the dominant sensorimotor cortex. All rats were randomly assigned into the ES group and control group. The behavioral test of a single pellet reaching task (SPRT) and neurological examinations including the Schabitz's photothrombotic neurological score and the Menzies test were conducted for 2 weeks. After 14 days, coronal sections were obtained and immunostained for neuronal cell differentiation markers including bromodeoxyuridine (BrdU), neuron-specific nuclear protein (NeuN), and doublecortin (DCX).

Results: On the SPRT, the motor function in paralytic forelimbs of the ES group was significantly improved. There were no significant differences in neurological examinations and neuronal cell differentiation markers except for the significantly increased number of DCX+ cells in the corpus callosum of the ES group (p<0.05). But in the ES group, the number of NeuN+ cells in the ischemic cortex and the number of NeuN+ cells and DCX+ cells in the ischemic striatum tended to increase. In the ES group, NeuN+ cells in the ischemic hemisphere and DCX+ cells and BrdU+ cells in the opposite hemisphere tended to increase compared to those in the contralateral.

Conclusion: The continuous epidural ES of the ischemic sensorimotor cortex induced a significant improvement in the motor function and tended to increase neural cell proliferation in the ischemic hemisphere and the neural regeneration in the opposite hemisphere.

Keywords: Cell proliferation; Cerebral ischemia; Electrical stimulation; Motor skills; Stroke.

Fig. 1

Seven regions (1-7) in a microscopic field (×200) of an interesting brain slice (+1.80 mm from the bregma, small brain at the bottom) for the measurement of ischemic area and immunostaining. The seven regions were: 1, ipsilateral peri-ischemic cortex; 2, ipsilateral adjacent peri-ischemic cortex; 3, contralateral adjacent peri-ischemic cortex; 4, contralateral peri-ischemic cortex; 5, ipsilateral striatum including the subventricular area; 6, contralateral striatum including the subventricular area; and 7, corpus callosum.

Fig. 2

Epidural electrical stimulation for 2 weeks after photothrombotic stroke enhanced the motor performance on single pellet reaching task (SPRT). ES, electrical stimulation; Control, the operation control group. ^*p<0.05 by Mann-Whitney U test between two groups. The comparison of the success rate between groups (p=0.047) and within the group (p<0.001) showed a significant difference in the analysis by repeated measures ANOVA.

Fig. 3

The neurological examinations including Schabitz's photothrombotic neurological score and Menzies test were performed for neurological evaluation of behavioral recovery. There were significant improvements in each neurological test for 2 weeks after photothrombotic stroke (p<0.05), but not between two groups at each test. ES, electrical stimulation; Cont, the operation control group.

Fig. 4

The immunohistochemical findings (×200) of doublecortin staining in the corpus callosum showed a significant increase in the number of neuroblasts (arrows) in the electrical stimulation group (A) than in the control group (B).