PDF(Pubmed)
Abstract：
Multiple sclerosis (MS) is a demyelinating central nervous system (CNS) disorder that is associated with functional impairment and accruing disability. There are multiple U.S. Food and Drug Administration (FDA)-approved drugs that effectively dampen inflammation and slow disability progression. However, these agents do not work well for all patients and are associated with side effects that may limit their use. The vagus nerve (VN) provides a direct communication conduit between the CNS and the periphery, and modulation of the inflammatory reflex via electrical stimulation of the VN (VNS) shows efficacy in ameliorating pathology in several CNS and autoimmune disorders. We therefore investigated the impact of VNS in a rat experimental autoimmune encephalomyelitis (EAE) model of MS. In this study, VNS-mediated neuroimmune modulation is demonstrated to effectively decrease EAE disease severity and duration, infiltration of neutrophils and pathogenic lymphocytes, myelin damage, blood-brain barrier disruption, fibrinogen deposition, and proinflammatory microglial activation. VNS modulates expression of genes that are implicated in MS pathogenesis, as well as those encoding myelin proteins and transcription factors regulating new myelin synthesis. Together, these data indicate that neuroimmune modulation via VNS may be a promising approach to treat MS, that not only ameliorates symptoms but potentially also promotes myelin repair (remyelination).
摘要：
多发性硬化症（MS）是一种脱髓鞘性中枢神经系统（CNS）疾病，与功能障碍和累积残疾有关。有多种美国食品和药物管理局（FDA）批准的药物可以有效抑制炎症并减缓残疾进展。然而,这些药物并非对所有患者都有效，并且伴随着可能限制其使用的副作用。迷走神经（VN）提供了中枢神经系统和外周之间的直接通信管道，和通过电刺激VN（VNS）调节炎性反射显示出改善几种CNS和自身免疫性疾病病理的功效。因此，我们研究了VNS在大鼠实验性自身免疫性脑脊髓炎（EAE）模型中的影响。在这项研究中,证明VNS介导的神经免疫调节可有效降低EAE疾病的严重程度和持续时间。嗜中性粒细胞和致病淋巴细胞浸润，髓鞘损伤,血脑屏障破坏,纤维蛋白原沉积，和促炎小胶质细胞激活。VNS调节与MS发病机制有关的基因的表达，以及编码髓鞘蛋白和调节新髓鞘合成的转录因子。一起,这些数据表明，通过VNS进行神经免疫调节可能是治疗MS的有希望的方法，这不仅可以改善症状，还可能促进髓鞘修复（髓鞘再生）。
