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经颅磁刺激对实验性自身免疫性脑脊髓炎脊髓 BDNF 表达的影响。

Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis.

机构信息

Institute of Medical Research, Military Medical Academy, Belgrade, Serbia.

Medical Faculty of Military Medical Academy, University of Defence, Serbia.

出版信息

Folia Neuropathol. 2019;57(2):129-145. doi: 10.5114/fn.2019.86294.

DOI:10.5114/fn.2019.86294
PMID:31556573
Abstract

Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins engaged in the activity of excitatory and inhibitory systems, restores these functions and suppresses the progression of disability in experimental autoimmune encephalitis (EAE). The structural type of TMS, the arrangement as theta burst stimulation (TBS) has been applied as intermittent TBS (iTBS) and continuous TBS (cTBS) protocols to female adult DA rats. The animals were randomly divided into experimental groups: control group (C), group treated with complete Freund's adjuvant (CFA), experimental autoimmune encephalomyelitis (EAE) group, group treated with iTBS post EAE immunization (EAE + iTBS), group treated with cTBS post EAE immunization (EAE + cTBS), group of healthy animals treated with iTBS or cTBS. Therapeutic protocols of iTBS or cTBS in all EAE groups of animals were performed starting from 14 days post immunization (dpi), for 10 days with time point decapitation at 24 dpi. After decapitation, spinal cords were analysed for BDNF and Ki67 expression. The results revealed reduced BDNF expression in the rat's spinal cord of EAE animals in the stage of remission, which was associated with increased Ki67 and GFAP expressions. Decreased Iba 1 and BDNF expression, contrary to increased Iba 1 and Ki67 expression, suggests clustered microglia in the resolution phase of EAE. Enhanced GABA expression in spinal cord sections indicates higher GABA metabolic turnover, and also GAD activity in astrocytes, or prominent activity of GABAergic neurons. Both TBS protocols induced advance BDNF expression; amongst iTBS application provoked elevating of BDNF and stabilizing of GFAP and Ki67 expressions.

摘要

重复经颅磁刺激(rTMS)可诱导参与兴奋性和抑制性系统活动的蛋白表达发生变化,恢复这些功能,并抑制实验性自身免疫性脑脊髓炎(EAE)的残疾进展。TMS 的结构类型,即 theta 爆发刺激(TBS)的排列方式,已应用于间歇性 TBS(iTBS)和连续 TBS(cTBS)方案,用于成年雌性 DA 大鼠。动物随机分为实验组:对照组(C)、完全弗氏佐剂(CFA)处理组、实验性自身免疫性脑脊髓炎(EAE)组、EAE 免疫后 iTBS 处理组(EAE+iTBS)、EAE 免疫后 cTBS 处理组(EAE+cTBS)、接受 iTBS 或 cTBS 治疗的健康动物组。所有 EAE 组动物的 iTBS 或 cTBS 治疗方案均从免疫后 14 天(dpi)开始进行,为期 10 天,在 24 dpi 时进行断头术。断头后,对脊髓进行 BDNF 和 Ki67 表达分析。结果显示,缓解期 EAE 大鼠脊髓 BDNF 表达减少,与 Ki67 和 GFAP 表达增加有关。Iba1 和 BDNF 表达减少,而 Iba1 和 Ki67 表达增加,提示 EAE 缓解期小胶质细胞呈簇状。脊髓切片中 GABA 表达增强表明 GABA 代谢周转率更高,星形胶质细胞中的 GAD 活性或 GABA 能神经元的突出活性。两种 TBS 方案均诱导 BDNF 表达提前;iTBS 应用可提高 BDNF 水平,并稳定 GFAP 和 Ki67 表达。

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