中国组织工程研究

中国组织工程研究 ›› 2014, Vol. 18 ›› Issue (27): 4368-4374.doi: 10.3969/j.issn.2095-4344.2014.27.017

• 器官移植动物模型 organ transplantation and animal model • 上一篇    下一篇

局灶性脑梗死模型大鼠予全植入式低强度皮质电刺激的安全和可行性

周  琴1，李明哲1，赵雪清1，李  涛1，段晏文2   

  1. 1武汉大学人民医院神经内科，湖北省武汉市  430060；2武汉大学化学与分子科学学院，湖北省武汉市  430073
  • 出版日期:2014-06-30 发布日期:2014-06-30
  • 通讯作者: 段晏文，博士，教授，博士生导师，武汉大学化学与分子科学学院，湖北省武汉市 430073
  • 作者简介:周琴，女，1982年生，湖北省应城市人，汉族，2009年武汉大学毕业，博士，主治医师，主要从事皮层电刺激和神经康复方面的研究。
  • 基金资助:

    国家自然科学基金-青年科学基金项目(81100983)

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

Zhou Qin1, Li Ming-zhe1, Zhao Xue-qing1, Li Tao1, Duan Yan-wen2   

  1. 1 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; 2 College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430073, Hubei Province, China
  • Online:2014-06-30 Published:2014-06-30
  • Contact: Duan Yan-wen, M.D., Professor, Doctoral supervisor, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430073, Hubei Province, China
  • About author:Zhou Qin, M.D., Attending physician, Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
  • Supported by:

    the National Natural Science Foundation of China for Youths, No. 81100983

PDF

369

被引次数

1

摘要：

背景：近10年来使用皮质电刺激治疗脑卒中的动物和临床试验均得到了比较肯定的结果。
目的：观察全植入式皮质电刺激器长时间、低强度、变频皮质电刺激对大鼠局灶性脑梗死后神经功能恢复的影响。
方法：成年雄性SD大鼠60只，线栓法制作大脑中动脉阻塞的脑梗死模型。选取Bederson评分为1-3分的大鼠40只进行MRI扫描，筛选出有皮质梗死的大鼠(n=23)，MRI测定梗死灶周边皮质的位点，确定接受皮质电刺激治疗的靶点，大脑中动脉阻塞后第6天植入电刺激器。将23只大鼠随机分为2组：皮质电刺激组(n=13)大鼠每天进行皮质电刺激治疗2次/d，每次持续30 min，电刺激频率10 s内在50，20和5 Hz之间变动并重复循环。无刺激组(n=10)仅植入电刺激器，无电刺激输出。在植入电刺激器后第2天和第16天，两组大鼠进行前肢使用不对称、足失误测试，第16天最后一次行为学评价完成后，取出电刺激器进行检测，常规苏木精-伊红染色观察大鼠梗死灶周围皮质结构及细胞形态。
结果与结论：23个电刺激器取出后，仅发现1个皮质电刺激组电刺激器不能正常工作，其余各电刺激器性能均保持良好。除1只大鼠在电刺激器植入部位的皮肤有破溃，愈合稍差，其余大鼠皮肤切口均愈合良好。苏木精-伊红染色可见脑梗死电极植入处皮质组织结构清晰完整，神经细胞排列整齐，神经元胞浆丰富，核仁清楚，正常胶质细胞结构完整，细胞周围间隙致密无水肿。足失误和前肢使用不对称测试结果均显示第16天皮质电刺激组大鼠神经功能恢复显著优于较无刺激组。结果表明采用了一套用于大鼠脑梗死模型的全植入式皮质电刺激器，建立了安全的植入方式及刺激模式，并证明低强度、长时间、变频的脉冲式电刺激模式是安全的，且有助于促进大脑局灶性脑梗死后的神经功能恢复。



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：

关键词: 动物模型, 组织构建, 皮质电刺激, 大脑中动脉阻塞, 植入式电刺激器, 安全电刺激, 电刺激模式, 国家自然科学基金

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

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