Neuroimmunology Clinic and Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology and Neuroimmunology Unit, Rabin Medical Center, Petah Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel..
Neuroimmunology Clinic and Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Neuroscience. 2023 Aug 1;524:89-93. doi: 10.1016/j.neuroscience.2023.05.027. Epub 2023 Jun 7.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of Inflammatory central nervous system (CNS) disease. Dark agouti (DA) rats immunized with full-length myelin oligodendrocyte glycoprotein (MOG) typically develop a relapsing-remitting EAE form characterized by predominant demyelinating involvement of the spinal cord and optic nerve. Visually evoked potentials (VEP) are a useful objective tool to assess the optic nerve function and monitor electrophysiological changes in optic neuritis (ON). The current study aimed to assess the VEP changes in MOG-EAE DA rats using a minimally invasive recording device and to correlate them with histological findings. Twelve MOG-EAE DA rats and four controls underwent VEP recording at day 0, 7, 14, 21, and 28 post-EAE induction. Tissue samples were obtained on days 14, 21, and 28 from two EAE rats and one control. The median VEP latencies were significantly higher on days 14, 21, and 28 compared to baseline, with maximal latencies observed on day 21. The histological analyses on day 14 demonstrated inflammation with largely preserved myelin and axonal structures. Inflammation and demyelination with largely preserved axons were evident on days 21 and 28, which correlated with prolonged VEP latencies. These findings suggest that VEPs may be a reliable biomarker reflecting the optic nerve involvement in EAE. Moreover, the use of a minimally invasive device enables observation of VEP changes over time in MOG-EAE DA rats. Our findings may have important implications for testing the potential neuroprotective and regenerative effects of new therapies for CNS demyelinating diseases.
实验性自身免疫性脑脊髓炎(EAE)是一种中枢神经系统(CNS)炎症性疾病的动物模型。全长髓鞘少突胶质细胞糖蛋白(MOG)免疫的深褐色(DA)大鼠通常会发展为复发性缓解型 EAE 形式,其特征是脊髓和视神经的脱髓鞘为主。视觉诱发电位(VEP)是一种有用的客观工具,可用于评估视神经功能并监测视神经炎(ON)中的电生理变化。本研究旨在使用微创记录设备评估 MOG-EAE DA 大鼠的 VEP 变化,并将其与组织学发现相关联。十二只 MOG-EAE DA 大鼠和四只对照大鼠在 EAE 诱导后第 0、7、14、21 和 28 天进行 VEP 记录。从两只 EAE 大鼠和一只对照大鼠中获得第 14、21 和 28 天的组织样本。与基线相比,第 14、21 和 28 天的 VEP 潜伏期明显升高,第 21 天观察到最长潜伏期。第 14 天的组织学分析显示炎症伴髓鞘和轴突结构基本保存。第 21 和 28 天观察到炎症和脱髓鞘伴大部分轴突保存,与 VEP 潜伏期延长相关。这些发现表明,VEP 可能是反映 EAE 视神经受累的可靠生物标志物。此外,使用微创设备可以观察到 MOG-EAE DA 大鼠中 VEP 随时间的变化。我们的发现可能对测试新的 CNS 脱髓鞘疾病治疗方法的潜在神经保护和再生作用具有重要意义。