恒河猴视神经脊髓炎模型神经网络重建对疾病预后预测研究

Neuromyelitis optica (NMO) is a severe, debilitating human disease that predominantly features immunopathology in the optic nerves and the spinal cord.Recently, some studies have reported abnormalities is not only in spinal cord and optic nerves.The NMO have occult damage in normal-appearing in brain tissue.We have also found such damage related with the congtive,disability and relapse in NMO patients.Diffusion tensor imaging values in the normal-appearing grey matter were found to be significantly different in the patients with NMO versus the healthy controls. But whether reconstruction brain network related to prognosis of NMO is unknown.However, it has still remained unclear whether there is a close relationship between biomarker and the prognosis of neuromyelitis optica (NMO).so we plan to induce the NMO model in rhesus. The aim of this study is to investigate the association between serum biomarker(AQP4，MOG,UA,IL-2, IFN-c, TNF, GM-CSF, IL-6) levels and disease activity in NMO.We also plan to use advanced magnetic resonance imaging (MRI) techniques to investigate whether have occult damage in brain and spinal cord in the rhesus NMO model.The techniques used on a 7.0T MRI imaging scanner were magnetization transfer imaging, diffusion tensor imaging,fMRI in order to reconstruction the network of brain and spinal.In our study we will continue to follow the NMO patients in order to find the relationship between the prognosis and the barin network.

视神经脊髓炎（NMO）是导致年轻人残疾的常见独立疾病，具有高致残率和高复发率。新近的研究发现NMO的损害不仅仅限于脊髓和视神经，而看似正常的脑也在早期即有损害。我们在前期的观察中发现NMO患者看似正常的脑组织损害与认知、残疾度、复发频率等因素存在一定相关性。但现有结果不能回答疾病演变过程中神经网络如何重建，以及神经网络重建如何与疾病预后相关。因此我们拟采用AQP4阳性患者IgG诱导建立恒河猴NMO模型，监测其免疫指标变化，同时利用7.0TMRI仪器采用高分辨率的弥散张量成像(DTI)和静息态功能磁共振成像技术（fMRI），探索性分割皮层和皮层下灰白质交界区、提取时间序列曲线等方法构建脑的解剖网络和功能网络。同时继续我们之前的NMO患者的随访观察，探索NMO患者认知和视觉障碍脑神经网络的"小世界"属性。期望为NMO患者的预后判断提供一定依据。

通过对系列视神经脊髓炎病人的3.0TMRIDTI及磁化转移技术研对视神经脊髓炎患者进了系列研究，结果显示：1. NMO白质纤维DTI成像显示NAWM的隐匿性病变，DTI、VEP及OCT三者之间具有显著的相关关系。2. NMO患者大脑灰白质磁化转移成像扫描显示MTR存在差异提示可能存在隐匿性损伤。这种隐匿性改变在急性期与稳定期可能存在差异。NMO患者大脑的隐匿性改变在MTI序列中可能与EDSS评分、病程及复发次数无关。3. 应用DTI对 NMO患者的定量研究提示：NMO患者的急性期与稳定期往往存在隐匿性差异。DTI在量化评估NMO患者脑组织损伤程度的中具有重要价值。 4.脊髓可能作为中枢性呃逆的激活中枢，其机制可能与炎性因子对膈神经中枢的刺激有关。