The safety and feasibility of a full-implanted cortical electrical stimulator with low-intensity stimulation in local cerebral infarction rats / 中国组织工程研究

ABSTRACT

BACKGROUND:Cortical electrical stimulation has achieved good effects in treatment of stroke through animal and clinical experiments. OBJECTIVE:To observe the effects of a ful y implanted cortical electrical stimulation device with long time, low intensity and various frequencies stimulation protocols on the neurological function recovery in a rat model of local cerebral infarction. METHODS:The cerebral infarction model was established through middle cerebral artery occlusion in 60 Sprague-Dawley adult male rats. Forty rats with 1-3 points by Bederson scale were detected with magnetic resonance imaging, which was used to confirm cortex infarction and to identify a location for implantation of stimulating electrode over the peri-infarct cortex. Twenty-three rats with cortex infarction were randomly divided into cortical electrical stimulation group (CES group, n=13) and no stimulation group (NS group;n=10). The device was implanted on 6 days after middle cerebral artery occlusion, and the stimulation was given for 16 days. The stimulation program consists of two sessions lasting half an hour each in the morning and in the afternoon respectively. Stimulator delivered biphasic charge balanced pulses (pulse width=200μs) with various frequencies of 50 Hz, 20 Hz and 5 Hz within 10 second blocks and then repeated. The rats of NS group were implanted with the device, but received no electrical stimulation. The behavioral tests, includingforelimb use asymmetry test and foot fault test were performed at 2 and 16 days after implantation. Final y, al of the devices were taken out to test if they were normal y working and al of the rats were sacrificed for hematoxylin-eosin staining, which can reflect the structure of peri-infarct cortex and cellmorphology. RESULTS AND CONCLUSION:There was only one stimulator in CES group cannot normal y work, and the remaining 22 ones worked wel . The skin covered the implanted stimulator was slightly ulcerated in one rat, and the incisions of the other rats were healed wel . Hematoxylin-eosin staining showed clear and intact structure in peri-infarction cortex (i.e., electrodes were implanted at the cortex), neurons arranged in neat rows, with abundant neuronal cytoplasm and clear nucleolus. The glial cells have complete structures, and there was no edema in the intercellular spaces. Foot-fault and forelimb use asymmetry tests showed the improved neurological function in rats of CES group than that of NS group. We designed a ful-implanted cortical electrical stimulator used in cerebral ischemic rats, and established an implanted method with long time, low intensity and various frequencies pulsed electrical stimulation. The results indicated the stimulation pattern in our study is safe and effective, and it can significantly promote functional recovery in local cerebral infarction rats.