The Effects Of Low-Intensity Of Cortical Electrical Stimulation On Functional Recovery After Focal Cerebral Ischemia In Rats

PART 1PURPOSE:Using magnetic resonance imaging, we investigated two different types of focal cerebral ischemia after 120 min middle cerebral artery occlusion (MCAO) by inserting a nylon filament in SD rats.METHODS:Thirty-three male SD rats were used in this study. The MCA were occlused by a nylon filament and the ischemic duration was 120 min. The rats with 1-3 scores of Bederson test were divided into two groups based on the different appearance on MRI:(1) lesions included cortex or cortex and basal ganglia (CBG group, n=11), (2) lesions restricted to the basal ganglia (BG group, n=12). Meanwhile, the rats with 0 score of Bederson test were also under the MRI examination to make sure there is no infaction occurred and these rats were then as the (3) no infarction group (NI group, n=10). Body weight was monitored every day and various behavioral tests (beam-walking, rota-rod, foot-fault, forelimb use asymmetry, and limb placement tests) were used to evaluate the neurologic deficits at 1,2,3,4,5,6 week after MCAO.RESULTS:Despite the infraction was developed, the rats of BG group did not show any sensorimotor deficits in all the time points. The percentage of body weight and the performance in all behavioral tests of rats in BG group have no significant difference compared to that of the rats in NI group (p>0.05). In contrast, rats of lesions included cortex (CBG) showed persisted neurologic deficits. At several time points in all behavioral tests, differences were significant between the rats of CBG and NI group. Except rota-rod test, the significant differences were also existed between the rats of CBG and BG group in the other behavioral tests.CONCLUSION:There were two totally different types of focal cerebral ischemia after 120 min MCAO in SD rats. The rats of lesions restricted to the basal ganglia did not show any sensorimotor deficits, at least at 1 week after MCAO, while the rats of lesions included cortex had persisted neurologic deficits. Thus, it is very import to identify these to different type to avoid complication of data analysis. PART 2PURPOSE:Using a fully implanted cortical electrical stimulation (CES) device with low-intensity stimulation protocol, we investigated the effects of CES alone on behavioral recovery in a rat model of middle cerebral artery occlusion (MCAO). Additionally, we also investigated the feasibility and safty of the fully implanted CES device.METHODS:After MCAO in rats, magnetic resonance imaging (MRI) was used to confirm cortex infarction and to identify a location for implantation of stimulating electrode over the peri-infarct cortex. The rats with cortex infaction (n=23) were randomly divided into (1) CES group (n=13) and (2) no stimulation (NS) group (n=10). The device was implanted on the 6th day after MCAO with CES then lasting for 16 days. The stimulation program consists of two sessions lasting half an hour each in the morning (current amplitude = 0.65 mA) and in the afternoon (current amplitude= 0.5 mA). Stimulator delivered biphasic charge balanced pulses (pulse width= 200?s) with various frequencies of 50 Hz,20 Hz and 5 Hz in 10 second blocks and then repeated. The rats of NS group were implanted the device but have no electrical stimulation. Body weight (BW) was monitored and behaviral tests were performed after 2,4,6,8,10,12,14 and 16 days after implantation surgery. Finally, all of the rats were sacrificed for immunohistochemistry.RESULTS:Rats with CES treatment spent much shorter time to regain preoperative levels of BW than those with no stimulation. In behavioral tests, the rats in CES group showed greater functional recovery compared to NS group in foot-fault and forelimb use asymmetry tests. Moreover, the functional improvement coincided with an increase in surface density of dendritic processes immunoreactive to microtubule-associated protein 2 (MAP2) in peri-infarction cortex (P<0.05), but this difference was disappeared in the contralateral and homotopic cortex to the lesion. Meanwhile, the cortical density of NeuN of CES group was not significantly different compared to the NS group.CONCLUSION:These results suggest the feasibility and the safty of the fully implanted CES device and the efficacy of the new stimulation protocol alone to improve functional outcome and cortical neuronal structural plasticity following focal cerebral ischemia in rats.