The safety and feasibility of a full-implanted cortical electrical stimulator with low-intensity stimulation in local cerebral infarction rats

doi:10.3969/j.issn.2095-4344.2014.27.017

Abstract

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 fully 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 = 200 μs) 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. Finally, all of the devices were taken out to test if they were normally working and all of the rats were sacrificed for hematoxylin-eosin staining, which can reflect the structure of peri-infarct cortex and cell morphology.
RESULTS AND CONCLUSION: There was only one stimulator in CES group cannot normally work, and the remaining 22 ones worked well. The skin covered the implanted stimulator was slightly ulcerated in one rat, and the incisions of the other rats were healed well. 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 full-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.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: occlusion, middle cerebral artery, electrical stimulation, cerebral cortex

CLC Number:

R318

Zhou Qin, Li Ming-zhe, Zhao Xue-qing, Li Tao, Duan Yan-wen. The safety and feasibility of a full-implanted cortical electrical stimulator with low-intensity stimulation in local cerebral infarction rats[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(27): 4368-4374.

Figures/Tables 2

References

[1]Harvey RL,Stinear JW.Cortical stimulation as an adjuvant to upper limb rehabilitation after stroke. PM R. 2010; 2 (12 Suppl 2):269-278.
[2]Hummel F, Celnik P, Pascual-Leone A,et al.Controversy: Noninvasive and invasive cortical stimulation show efficacy in treating stroke patients.Brain Stimulation.2008;1:370-382.
[3]Peterchev AV, Wagner TA, Miranda PC,et al.Fundamentals of Transcranial Electric and Magnetic Stimulation Dose: Definition, Selection, and Reporting Practices. Brain Stimul. 2012;5(4):435-453.
[4]Brunoni AR, Nitsche MA, Bolognini N, et al. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul.2012;5(3):175-195.
[5]Li Q, Qian ZM, Arbuthnott GW, et al. Cortical effects of deep brain stimulation: implications for pathogenesis and treatment of Parkinson disease. JAMA Neurol. 2014;71(1):100-103.
[6]Brown JA, Lutsep H, Cramer SC,et al. Motor cortex stimulation for enhancement of recovery after stroke: Case report.Neurol Res.2003;25:815-818.
[7]Brown JA, Lutsep HL, Weinand M,et al. Motor cortex stimulation for the enhancement of recovery from stroke: A prospective, multicenter safety study. Neurosurgery.2006; 58:464-473.
[8]Huang M, Harvey RL, Stoykov ME,et al.Cortical stimulation for upper limb recovery following ischemic stroke: A small phase ii pilot study of a fully implanted stimulator. Top Stroke Rehabil. 2008;15:160-172.
[9]Kim HI, Shin YI, Moon SK,et al. Unipolar and continuous cortical stimulation to enhance motor and language deficit in patients with chronic stroke: Report of 2 cases. Surg Neurol. 2008;69:77-80.
[10]Levy R, Ruland S, Weinand M,et al.Cortical stimulation for the rehabilitation of patients with hemiparetic stroke: A multicenter feasibility study of safety and efficacy.J Neurosurg.2008; 108: 707-714.
[11]Koesler IB, Dafotakis M,Ameli M,et al.Electrical somatosensory stimulation improves movement kinematics of the affected hand following stroke. J Neurol Neurosurg Psychiatry.2009;80(6): 614-619.
[12]Adkins-Muir DL, Jones TA. Cortical electrical stimulation combined with rehabilitative training: Enhanced functional recovery and dendritic plasticity following focal cortical ischemia in rats. Neurol Res.2003;25:780-788.
[13]Kleim JA, Bruneau R, VandenBerg P, et al. Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult. Neurol Res.2003; 25: 789-793.
[14]Plautz EJ, Barbay S, Frost SB, et al. Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: A feasibility study in primates.Neurol Res.2003;25:801-810.
[15]Teskey GC, Flynn C, Goertzen CD,et al.Cortical stimulation improves skilled forelimb use following a focal ischemic infarct in the rat. Neurol Res.2003;25:794-800.
[16]Adkins DL, Campos P, Quach D,et al. Epidural cortical stimulation enhances motor function after sensorimotor cortical infarcts in rats. Exp Neurol.2006;200:356-370.
[17]Adkins DL, Hsu JE, Jones TA.Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions. Exp Neurol.2008; 212: 14-28.
[18]Nouri S, Cramer SC. Anatomy and physiology predict response to motor cortex stimulation after stroke. Neurology. 2011;77(11):1076-1083.
[19]Moon SK, Shin YI, Kim HI, et al.Effect of prolonged cortical stimulation differs with size of infarct after sensorimotor cortical lesions in rats. Neurosci Lett.2009;460(2):152-155.
[20]Baba T, Kameda M, Yasuhara T, et al. Electrical stimulation of the cerebral cortex exerts antiapoptotic, angiogenic, and anti-inflammatory effects in ischemic stroke rats through phosphoinositide 3-kinase/Akt signaling pathway. Stroke.2009; 40(11):e598-605.
[21]Cogan SF. Neural stimulation and recording electrodes. Annu Rev Biomed Eng. 2008;10:275-309.
[22]Winter JO, Cogan SF, Rizzo JF, 3rd. Retinal prostheses: Current challenges and future outlook. J Biomater Sci Polym Ed. 2007;18(8):1031-1055.
[23]Longa EZ, Weinstein PR, Carlson S,et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20:84-91.
[24]张乾,毛善平,李涛,等.构建大脑中动脉阻塞脑缺血模型大鼠的类型分析[J].中国组织工程研究与临床康复,2011,15(24):4391- 4394.
[25]Wegener S, Weber R, Ramos-Cabrer P, et al. Subcortical lesions after transient thread occlusion in the rat: T2-weighted magnetic resonance imaging findings without corresponding sensorimotor deficits.J Magn Reson Imaging.2005;21: 340-346.
[26]Schaar KL, Brenneman MM, Savitz SI. Functional assessments in the rodent stroke model.Exp Transl Stroke Med.2010;2(1):13.
[27]Cheng X, Li T, Zhou H, Zhang Q, et al. Cortical electrical stimulation with varied low frequencies promotes functional recovery and brain remodeling in a rat model of ischemia. Brain Res Bull. 2012;89(3-4):124-132.