Marenna Silvia, Huang Su-Chun, Dalla Costa Gloria, d'Isa Raffaele, Castoldi Valerio, Rossi Elena, Comi Giancarlo, Leocani Letizia
Experimental Neurophysiology Unit, Institute of Experimental Neurology (INSPE), IRCCS-Scientific Institute San Raffaele, Milan, Italy.
Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
Front Neurosci. 2022 Apr 15;16:820155. doi: 10.3389/fnins.2022.820155. eCollection 2022.
The visual system is one of the most accessible routes to study the central nervous system under pathological conditions, such as in multiple sclerosis (MS). Non-invasive visual evoked potential (VEP) and optical coherence tomography (OCT) were used to assess visual function and neuroretinal thickness in C57BL/6 taking 0.2% cuprizone for 7 weeks and at 5, 8, 12, and 15 days after returning to a normal diet. VEPs were significantly delayed starting from 4 weeks on cuprizone, with progressive recovery off cuprizone, becoming significant at day 8, complete at day 15. In contrast, OCT and neurofilament staining showed no significant axonal thinning. Optic nerve histology indicated that whilst there was significant myelin loss at 7 weeks on the cuprizone diet compared with healthy mice, at 15 days off cuprizone diet demyelination was significantly less severe. The number of Iba 1 cells was found increased in cuprizone mice at 7 weeks on and 15 days off cuprizone. The combined use of VEPs and OCT allowed us to characterize non-invasively, , the functional and structural changes associated with demyelination and remyelination in a preclinical model of MS. This approach contributes to the non-invasive study of possible effective treatments to promote remyelination in demyelinating pathologies.
视觉系统是在病理条件下(如多发性硬化症,MS)研究中枢神经系统的最便捷途径之一。使用非侵入性视觉诱发电位(VEP)和光学相干断层扫描(OCT)来评估C57BL/6小鼠在摄入0.2%的铜螯合剂7周后以及恢复正常饮食后第5、8、12和15天的视觉功能和神经视网膜厚度。从摄入铜螯合剂4周开始,VEP明显延迟,停止摄入铜螯合剂后逐渐恢复,在第8天变得显著,在第15天完全恢复。相比之下,OCT和神经丝染色显示轴突没有明显变细。视神经组织学表明,与健康小鼠相比,在摄入铜螯合剂饮食7周时存在明显的髓鞘损失,而在停止摄入铜螯合剂饮食15天时,脱髓鞘程度明显减轻。发现摄入铜螯合剂7周时和停止摄入铜螯合剂15天时,铜螯合剂小鼠中Iba 1细胞数量增加。VEP和OCT的联合使用使我们能够在MS临床前模型中以非侵入性方式表征与脱髓鞘和髓鞘再生相关的功能和结构变化。这种方法有助于对促进脱髓鞘疾病中髓鞘再生的可能有效治疗方法进行非侵入性研究。