Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair.
Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair.
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DOI：
10.1016/j.jneumeth.2017.04.003
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发表时间：
2017-06-01
影响因子：
3
通讯作者：
Tiwari-Woodruff SK
中科院分区：
文献类型：
--
作者：
Hasselmann JPC;Karim H;Khalaj AJ;Ghosh S;Tiwari-Woodruff SK
虽然许多研究小组使用实验性自身免疫性脑脊髓炎（EAE）作为模型来揭示治疗靶点并了解多发性硬化症（MS）的病理学基础，但EAE方案的可变性导致中枢神经系统（CNS）发病机制和临床疾病的差异，限制了研究之间的可比性并减缓了急需的转化研究。在这里，我们描述了一个详细的，可靠的协议慢性EAE诱导C57 BL/6小鼠利用两次注射髓鞘少突胶质细胞糖蛋白（35-55）肽混合完全弗氏佐剂和百日咳毒素配对。本文提出的活性MOG 35 -55 EAE方案在80-100%的诱导小鼠中诱导上行性麻痹。我们注意到：（1）一致的T细胞免疫活化，（2）外周免疫细胞的强CNS浸润，和（3）血管周围脱髓鞘病变，同时伴有脊髓和各种脑区域（包括视神经、皮质、海马、内囊和小脑）中的轴突损伤。缺乏详细的方案，加上实验室之间的差异，使得EAE结果难以比较，并阻碍了该模型用于治疗开发。我们提供迄今为止最详细的主动MOG 35 -55-EAE协议。通过该方案，我们观察到高发病率和一致、可靠的病程。所产生的病理学是MS样的，包括视神经炎、血管周围单核细胞浸润、CNS轴突脱髓鞘和浸润性病变和其他正常外观的白色物质中的轴突损伤。通过提供一个详细的活性MOG 35 -55-EAE方案，产生一致和强大的病理学，我们的目标是促进临床前研究之间的可比性，并促进MS治疗的发现。
While many groups use experimental autoimmune encephalomyelitis (EAE) as a model to uncover therapeutic targets and understand the pathology underlying multiple sclerosis (MS), EAE protocol variability introduces discrepancies in central nervous system (CNS) pathogenesis and clinical disease, limiting the comparability between studies and slowing much-needed translational research. Here we describe a detailed, reliable protocol for chronic EAE induction in C57BL/6 mice utilizing two injections of myelin oligodendrocyte glycoprotein (35–55) peptide mixed with Complete Freund’s Adjuvant and paired with pertussis toxin. The active MOG35–55 EAE protocol presented here induces ascending paralysis in 80–100% of induced mice. We observe: (1) consistent T cell immune activation, (2) robust CNS infiltration by peripheral immune cells, and (3) perivascular demyelinating lesions concurrent with axon damage in the spinal cord and various brain regions, including the optic nerve, cortex, hippocampus, internal capsules, and the cerebellum. Lack of detailed protocols, combined with variability between laboratories, make EAE results difficult to compare and hinder the use of this model for therapeutic development. We provide the most detailed active MOG35–55-EAE protocol to date. With this protocol, we observe high disease incidence and a consistent, reliable disease course. The resulting pathology is MS-like and includes optic neuritis, perivascular mononuclear infiltration, CNS axon demyelination, and axon damage in both infiltrating lesions and otherwise normal-appearing white matter. By providing a detailed active MOG35–55-EAE protocol that yields consistent and robust pathology, we aim to foster comparability between pre-clinical studies and facilitate the discovery of MS therapeutics.
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影响因子：
4.3
作者：
Dias, Alyria Teixeira;Ribeiro De Castro, Sandra Bertelli;Ferreira, Ana Paula
通讯作者：
Ferreira, Ana Paula
影响因子：
4.7
作者：
Boullerne, Anne I.;Polak, Paul E.;Feinstein, Douglas L.
通讯作者：
Feinstein, Douglas L.
影响因子：
100.3
作者：
Baxter, Alan G.
通讯作者：
Baxter, Alan G.
影响因子：
6
作者：
Ghezzi, A;Martinelli, V;Canal, N
通讯作者：
Canal, N
DOI：
10.1073/pnas.0813312106
发表时间：
2009-03-31
影响因子：
11.1
作者：
Becklund, Bryan R.;Hansen, Donald W., Jr.;DeLuca, Hector F.
通讯作者：
DeLuca, Hector F.