Anti-inflammatory cytokine gene therapy decreases sensory and motor dysfunction in experimental Multiple Sclerosis: MOG-EAE behavioral and anatomical symptom treatment with cytokine gene therapy.
Anti-inflammatory cytokine gene therapy decreases sensory and motor dysfunction in experimental Multiple Sclerosis: MOG-EAE behavioral and anatomical symptom treatment with cytokine gene therapy.
复制标题
DOI：
10.1016/j.bbi.2008.09.004
复制
发表时间：
2009-01
影响因子：
15.1
通讯作者：
Van Dam, A. M.
中科院分区：
文献类型：
--
作者：
Sloane, Evan;Ledeboer, A.;Seibert, W.;Coats, B.;van Strien, M.;Maier, S. F.;Johnson, K. W.;Chavez, R.;Watkins, L. R.;Leinwand, L.;Milligan, E. D.;Van Dam, A. M.
多发性硬化症（MS）是一种自身免疫性炎性疾病，其临床表现为一系列症状，包括运动、感觉和认知功能障碍以及脑和脊髓中的脱髓鞘和病变形成。已经开发了多种MS动物模型，其具有MS的许多病理学特征，包括运动缺陷（上行性麻痹）、脱髓鞘和中枢神经系统（CNS）组织的轴突损伤。近年来，神经病理性疼痛已被认为是大多数MS患者的常见症状。到目前为止，已经有很少的调查感觉障碍的MS动物模型。目前的工作包括第一次评估后爪机械异常性疼痛（冯弗雷测试）的过程中复发缓解型髓鞘少突胶质细胞糖蛋白诱导的实验性自身免疫性脑脊髓炎（MOG-EAE）的MS大鼠模型，并建立了该模型的实用程序在检查自身免疫诱导的感觉功能障碍。我们证明了两个降低的反应性触摸后肢麻痹的发病之前，和增加的反应性（异常性疼痛），发生在传统上被称为症状缓解的运动缺陷改善期间的时期。此外，我们测试了我们最近表征的抗炎IL-10基因疗法治疗自身免疫性炎症诱导的行为症状和组织组织病理学变化的能力。本文显示该疗法逆转炎症诱导的麻痹，减少与疾病相关的对触摸的敏感性降低，预防异常性疼痛的发作，逆转与疾病相关的体重减轻，并抑制与该模型中的疾病进展相关的CNS神经胶质活化。
Multiple Sclerosis (MS) is an autoimmune inflammatory disease that presents clinically with a range of symptoms including motor, sensory, and cognitive dysfunction as well as demyelination and lesion formation in brain and spinal cord. A variety of animal models of MS have been developed that share many of the pathological hallmarks of MS including motor deficits (ascending paralysis), demyelination and axonal damage of central nervous system (CNS) tissue. In recent years, neuropathic pain has been recognized as a prevalent symptom of MS in a majority of patients. To date, there have been very few investigations into sensory disturbances in animal models of MS. The current work contains the first assessment of hind paw mechanical allodynia (von Frey test) over the course of a relapsing-remitting myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE) rat model of MS and establishes the utility of this model in examining autoimmune induced sensory dysfunction. We demonstrate periods of both decreased responsiveness to touch that precedes the onset of hind limb paralysis, and increased responsiveness (allodynia) that occurs during the period of motor deficit amelioration traditionally referred to as symptom remission. Furthermore, we tested the ability of our recently characterized anti-inflammatory IL-10 gene therapy to treat the autoimmune inflammation induced behavioral symptoms and tissue histopathological changes. This therapy is shown here to reverse inflammation induced paralysis, to reduce disease associated reduction in sensitivity to touch, to prevent the onset of allodynia, to reverse disease associated loss of body weight, and to suppress CNS glial activation associated with disease progression in this model.
登录
查看更多内容
影响因子：
6.4
作者：
Gray, Elizabeth;Thomas, Taya L.;Love, Seth
通讯作者：
Love, Seth
影响因子：
7.4
作者：
Hadjimichael, Olympia;Kerns, Robert D.;Vollmer, Timothy
通讯作者：
Vollmer, Timothy
DOI：
10.1073/pnas.0404887101
发表时间：
2004-10-05
影响因子：
11.1
作者：
Arnon, R;Aharoni, R
通讯作者：
Aharoni, R
影响因子：
2.5
作者：
Cunningham, AJ;Murray, CA;OConnor, JJ
通讯作者：
OConnor, JJ
影响因子：
3.3
作者：
Kenealy, SJ;Pericak-Vance, MA;Haines, JL
通讯作者：
Haines, JL