| 邓维维,闵令霞,冯 州,侯景明,刘宏亮.光遗传学靶向激活M1区谷氨酸能神经元促进脊髓损伤大鼠运动功能恢复的初步研究[J].中国康复医学杂志,2021,(5):520~525 |
| 光遗传学靶向激活M1区谷氨酸能神经元促进脊髓损伤大鼠运动功能恢复的初步研究 点此下载全文 |
| 邓维维 闵令霞 冯 州 侯景明 刘宏亮 |
| 陆军军医大学西南医院康复科，全军创伤疾病康复治疗中心，重庆市，400038 |
| 基金项目：国家自然科学基金项目(81671211，81672251)；西南医院优秀人才基金项目（2017MPRC—08，SWH2016JSYB—08） |
| DOI：10.3969/j.issn.1001-1242.2021.05.003 |
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| 摘要
目的：观察光遗传学靶向激活M1区谷氨酸能神经元对脊髓损伤（SCI）大鼠运动功能恢复的影响。
方法：24只雌性SD大鼠随机分为3组：单纯SCI组（8只），光刺激组（8只）和假刺激组（8只）。应用钳夹法制备大鼠SCI模型。单纯SCI组仅行SCI造模，不作任何干预；光刺激组利用光遗传学技术精确激活SCI大鼠双侧M1区谷氨酸能神经元；假刺激组植入的病毒中不含光敏感蛋白，利用光遗传学技术无法激活谷氨酸能神经元。光刺激组和假刺激组大鼠于造模成功后第3—14天进行470nm蓝光刺激，每日2次，共刺激2周。采用BBB评分和斜坡实验在造模后1—8周时每周评价SCI大鼠的运动功能。在SCI造模后第4周时每组取2只大鼠的脊髓组织进行HE染色观察损伤区域脊髓的修复情况。
结果：实验期间通过光遗传学技术刺激SCI大鼠M1区谷氨酸能神经元总体是安全的。BBB评分和斜坡实验显示，光刺激组SCI大鼠的运动功能从SCI后第2周开始明显要优于单纯SCI组和假刺激组（P<0.01），其中第4周时光刺激组的BBB评分与其余2组差异最明显（P<0.001）。单纯SCI组和假刺激组在各时间点的BBB评分和斜坡实验评分均无明显差异（P>0.05）。SCI造模后第4周时HE染色显示光刺激组脊髓组织的恢复情况明显优于单纯SCI组和假刺激组。
结论：M1区的谷氨酸能神经元在SCI大鼠功能恢复中起着重要作用，未来可以作为一个重要的干预靶点进行深入研究。 |
| 关键词：脊髓损伤 光遗传学 初级运动皮层 谷氨酸能神经元 运动康复 |
| A preliminary study on effects of optogenetic stimulation of glutamate neurons in the M1 region on the functional recovery of rats with spinal cord injury Download Fulltext |
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| Department of Rehabilitation，Southwest Hospital，Army Medical University，Chongqing，400038 |
| Fund Project: |
| Abstract: |
| Abstract
Objective： To investigate the effects of optogenetic stimulation of glutamate neurons in the M1 region on motor function recovery in spinal cord injury (SCI) rats.
Method： The 24 female SD rats were randomly divided into 3 groups： pure SCI group (n=8)， stimulation group (n=8) and false stimulation group (n=8). Rat model of T10 spinal cord injury was prepared by clamping method. The pure SCI group only underwent spinal cord injury modeling without any intervention. The stimulation group was given optogenetics to precisely activate glutamate neurons in bilateral M1 region of rats with SCI. The virus implanted in the false stimulation group did not contain light-sensitive proteins and could not activate glutamate neurons using optogenetics. The fiber embedded in the M1 zone of SCI rats was stimulated by 470nm blue light after the successful modeling， twice a day for 2 weeks continuously. BBB score and ramp test were used to evaluate the motor function of SCI rats at 1 to 8 weeks of treatment. Repair of spinal cord injury was observed by HE staining at 4 weeks.
Result： The BBB scores showed that the motor function of each group increased with the extension of time， but the BBB score of the light stimulation group was higher than that of the pure SCI group and the false stimulation group (P<0.01).Slope experiment showed that the slope angle of the light stimulation group was higher than that of the SCI group and the false stimulation group every week (P<0.001).HE staining showed that the recovery of spinal cord tissue in the light stimulation group was significantly better than that in the pure SCI group and the false stimulation group.
Conclusion： Optogenetic activation of glutamate-energy neurons in M1 region selectively can ameliorate the recovery of injured spinal cord tissue， thus promote the motor function recovery of SCI rats. |
| Keywords:spinal cord injury optogenetics primary motor cortex glutamatergic neuron motor recovery |
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