基于低频聚焦超声联合微泡技术的视神经脊髓炎动物模型的构建及鉴定

Neuromyelitis optica (NMO) is an acute or subacute autoimmune inflammatory disease in the central nervous system (CNS) associated with the first inflammatory demyelinating lesions mainly in optic nerve and spinal cord, with high prevalence throughout Asian population. Our previous study successfully developed spontaneous isolated optic neuritis animal models of incidence with myelin oligodendrocyte glycoprotein (MOG)-specific T cell receptor (TCR) transgenic mice. Then we plan to use MOG-specific TCR transgenic mice involved administration of human anti-aquaporin-4 immunoglobulin G antibody with complement to open its blood-brain barrier noninvasively by "low-frequency focused ultrasound combined with microbubble technology" to construct NMO transgenic animal model which objectively reflect the natural process of NMO. Basing on optical characteristics, visual separation features, changes of optic pathway and visal cortex electrophysiology, we tend to establish a new comprehensive evaluation system of visual function to present the real visual impairment of NMO. In summary, this NMO animal model integrating environmental and genetic factors may be more objectively reflect the pathophysiology of NMO than traditional animal models, and it will provide new experimental platform and tools for the pathogenesis and prevention of NMO in the future.

视神经脊髓炎（neuromyelitis optica, NMO）是一种视神经与脊髓同时或相继受累的急性或亚急性自身免疫性脱髓鞘疾病，其发病率在亚洲人群中较高。我们曾采用髓鞘少突胶质细胞糖蛋白（myelin oligodendrocyte glycoprotein, MOG）特异的T细胞受体（TCR）转基因小鼠成功诱导自发性孤立性视神经炎动物模型。本项目拟以MOG-TCR转基因小鼠为研究对象，采用"低频聚焦超声联合微泡技术"无创、短暂、可逆性开放血脑屏障，用水通道蛋白4-IgG及补体免疫诱导建立改良NMO转基因小鼠模型；拟结合视觉光学特性和图形区域分离特点及视神经通路、视皮层电生理改变等，探索建立新的视觉功能损伤评价体系，更全面反映视觉通路损害部位及程度。该模型较传统NMO动物模型，综合了环境和遗传因素，可能更客观反映NMO的病理生理过程，为深入研究NMO的发病机制及防治提供新的研究工具。

视神经脊髓炎（neuromyelitis optica, NMO）是一种视神经与脊髓同时或相继受累的急性或亚急性自身免疫性脱髓鞘疾病，其发病率在亚洲人群中较高。目前尚无普遍认可的NMO动物模型。我们在工作中按照既定的目标，完成了以下的工作：1. 我们成功提取了NMO-IgG及补体；2.采用“低频聚焦超声联合微泡技术”无创、短暂、可逆性开放血脑屏障；3.用NMO-IgG及补体免疫诱导联合血脑屏障开放建立改良NMO模型，并进行病理学及免疫学评估。我们发现，57.5%小鼠视神经出现炎细胞浸润、脱髓鞘，免疫荧光示视神经GFAP和AQP4的局部脱失。该模型较传统NMO动物模型可能更客观反映NMO的病理生理过程，为深入研究NMO的发病机制及防治提供新的研究工具。