Madsen Pernille M, Sloley Stephanie S, Vitores Alberto A, Carballosa-Gautam Melissa M, Brambilla Roberta, Hentall Ian D
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, USA; Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, USA.
Neuroscience. 2017 Mar 27;346:395-402. doi: 10.1016/j.neuroscience.2017.01.037. Epub 2017 Jan 29.
Multiple sclerosis (MS), a neuroinflammatory disease, has few treatment options, none entirely adequate. We studied whether prolonged electrical microstimulation of a hindbrain region (the nucleus raphe magnus) can attenuate experimental autoimmune encephalomyelitis, a murine model of MS induced by MOG injection. Eight days after symptoms emerged, a wireless electrical stimulator with an attached microelectrode was implanted cranially, and daily intermittent stimulation was begun in awake, unrestrained mice. The thoracic spinal cord was analyzed for changes in histology (on day 29) and gene expression (on day 37), with a focus on myelination and cytokine production. Controls, with inactive implants, showed a phase of disease exacerbation on days 19-25 that stimulation for >16days eliminated. Prolonged stimulation also reduced numbers of infiltrating immune cells and increased numbers of myelinated axons. It additionally lowered genetic expression of some pro-inflammatory cytokines (interferon gamma and tumor necrosis factor) and platelet-derived growth factor receptor alpha, a marker of oligodendrocyte precursors, while raising expression of myelin basic protein. Studies of restorative treatments for MS might profitably consider ways to stimulate the raphe magnus, directly or via its inputs, or to emulate its serotonergic and peptidergic output.
多发性硬化症（MS）是一种神经炎症性疾病，治疗选择有限，且无一完全令人满意。我们研究了对后脑区域（中缝大核）进行长时间电微刺激是否能减轻实验性自身免疫性脑脊髓炎，这是一种通过注射髓鞘少突胶质细胞糖蛋白（MOG）诱导的MS小鼠模型。症状出现8天后，将带有微电极的无线电刺激器植入颅骨，并在清醒、不受束缚的小鼠中开始每日间歇性刺激。对胸段脊髓进行组织学变化（第29天）和基因表达（第37天）分析，重点关注髓鞘形成和细胞因子产生。植入物无活性的对照组在第19 - 25天出现疾病加重阶段，而超过16天的刺激消除了这一阶段。长时间刺激还减少了浸润免疫细胞数量，增加了有髓轴突数量。此外，它降低了一些促炎细胞因子（干扰素γ和肿瘤坏死因子）以及少突胶质细胞前体标志物血小板衍生生长因子受体α的基因表达，同时提高了髓鞘碱性蛋白的表达。对MS恢复性治疗的研究可能会有益地考虑直接刺激中缝大核或通过其输入进行刺激的方法，或者模拟其血清素能和肽能输出。
