Transcranial Intermittent Theta-Burst Stimulation Reverses Neurodegeneration in the Somatosensory Motor Cortex after Spinal Cord Transection in Rats.

IF 2.5 4区 医学 Q3 NEUROSCIENCES
Zhenghong Chen, Yujian Lin, Jing Xu, Jiawei Sun, Rui Liu, Yue Yang, Zhen Chen, Mingyu Lv, Biqin Lai, Ling Zhang
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Abstract

Background: Complete spinal cord injury (SCI) leads to a disconnection between the brain and the body below the injury level, resulting in the functional silencing, degeneration, and apoptosis of sensorimotor cortex (SMC) neurons, which is of crucial importance to the pathological process.

Methods: In this study, a rat model of spinal cord transection was employed to explore the activation of neurons in the SMC and the reversal of neurodegeneration after the rats were treated with transcranial intermittent theta-burst stimulation (T-iTBS).

Results: The results demonstrated that the expression of the immediate early gene c-Fos and the synaptic plasticity-associated activity-regulated cytoskeleton (Arc) gene in the neurons of the SMC was increased in the T-iTBS group 4 weeks after SCI. Transcriptome sequencing revealed that neuronal activation-, neuronal metabolism-, synaptic activity-, and neural regeneration-related genes were significantly upregulated in the T-iTBS group compared with those of the sham-iTBS group, but the expression was similar to that in the normal group. Western blot analysis indicated that the expression of Cle-caspase-3 (CC3) in the SMC was significantly reduced in the T-iTBS group, and the number of CD68-positive cells in the SMC was close to that of normal rats but significantly less than that in the sham-iTBS and SCI groups. These results are in line with those of the transcriptome sequencing. Correlation analysis of the expression rate between c-Fos and Arc, CC3, and CD68 further suggested that T-iTBS improved the immune microenvironment and prevented neurodegeneration by regulating the activation and synaptic plasticity of SMC neurons in the early stages of injury.

Conclusions: Collectively, our findings offer support for the utilization of T-iTBS, a non-invasive neural stimulation treatment, to prevent SMC degeneration following severe SCI.

经颅间歇性θ - burst刺激逆转大鼠脊髓横断后体感觉运动皮质神经退行性变。
背景:完全性脊髓损伤(Complete spinal cord injury, SCI)导致损伤水平以下脑与体之间的连接断开,导致感觉运动皮层(sensorimotor cortex, SMC)神经元的功能沉默、变性和凋亡,在病理过程中起着至关重要的作用。方法:采用大鼠脊髓横断模型,探讨经颅间歇性θ -burst刺激(T-iTBS)对大鼠脊髓内SMC神经元的激活及神经退行性变的逆转作用。结果:结果显示,脊髓损伤后4周,T-iTBS组SMC神经元中即时早期基因c-Fos和突触可塑性相关活性调节细胞骨架(Arc)基因的表达增加。转录组测序结果显示,与sham-iTBS组相比,T-iTBS组神经元活化-、神经元代谢-、突触活性-和神经再生相关基因显著上调,但表达与正常组相似。Western blot分析显示,T-iTBS组SMC中Cle-caspase-3 (CC3)的表达明显降低,SMC中cd68阳性细胞数量与正常大鼠相近,但明显少于sham-iTBS和SCI组。这些结果与转录组测序结果一致。c-Fos与Arc、CC3、CD68表达率的相关性分析进一步表明,T-iTBS通过调节损伤早期SMC神经元的激活和突触可塑性,改善免疫微环境,防止神经退行性变。结论:总的来说,我们的研究结果为使用T-iTBS(一种非侵入性神经刺激治疗)来预防严重脊髓损伤后的SMC变性提供了支持。
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来源期刊
CiteScore
2.80
自引率
5.60%
发文量
173
审稿时长
2 months
期刊介绍: JIN is an international peer-reviewed, open access journal. JIN publishes leading-edge research at the interface of theoretical and experimental neuroscience, focusing across hierarchical levels of brain organization to better understand how diverse functions are integrated. We encourage submissions from scientists of all specialties that relate to brain functioning.
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