Research Unit of Experimental Neurotraumatology, Department of Neurosurgery, Medical University Graz.
Department of Neurology, Medical University Graz.
J Vis Exp. 2021 Sep 21(175). doi: 10.3791/57879.
Multiple sclerosis (MS) is the most common immune-mediated disease of the central nervous system (CNS) and progressively leads to physical disability and death, caused by white matter lesions in the spinal cord and cerebellum, as well as by demyelination in grey matter. Whilst conventional models of experimental allergic encephalomyelitis are suitable for the investigation of the cell-mediated inflammation in the spinal and cerebellar white matter, they fail to address grey matter pathologies. Here, we present the experimental protocol for a novel rat model of cortical demyelination allowing the investigation of the pathological and molecular mechanisms leading to cortical lesions. The demyelination is induced by an immunization with low-dose myelin oligodendrocyte glycoprotein (MOG) in an incomplete Freund's adjuvant followed by a catheter-mediated intracerebral delivery of pro-inflammatory cytokines. The catheter, moreover, enables multiple rounds of demyelination without causing injection-induced trauma, as well as the intracerebral delivery of potential therapeutic drugs undergoing a preclinical investigation. The method is also ethically favorable as animal pain and distress or disability are controlled and relatively minimal. The expected timeframe for the implementation of the entire protocol is around 8 - 10 weeks.
多发性硬化症（MS）是最常见的中枢神经系统（CNS）免疫介导疾病，逐渐导致身体残疾和死亡，其病因是脊髓和小脑的白质病变，以及灰质的脱髓鞘。虽然实验性变应性脑脊髓炎的传统模型适合研究脊髓和小脑白质中的细胞介导炎症，但它们无法解决灰质病变。在这里，我们提出了一种新的大鼠皮质脱髓鞘模型的实验方案，该模型可用于研究导致皮质病变的病理和分子机制。脱髓鞘是通过用低剂量髓鞘少突胶质细胞糖蛋白（MOG）在不完全弗氏佐剂中免疫诱导，然后通过导管介导将促炎细胞因子递送至脑内引起的。此外，导管还可以在不引起注射引起的创伤的情况下进行多次脱髓鞘，并且可以递送至正在进行临床前研究的潜在治疗性药物。该方法在伦理学上也具有优势，因为可以控制和减轻动物的疼痛、不适或残疾。整个方案的实施预计需要 8-10 周的时间。
