Focal Immune-Mediated White Matter Demyelination Reveals an Age-Associated Increase in Axonal Vulnerability and Decreased Remyelination Efficiency
Focal Immune-Mediated White Matter Demyelination Reveals an Age-Associated Increase in Axonal Vulnerability and Decreased Remyelination Efficiency
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DOI：
10.1016/j.ajpath.2012.01.018
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发表时间：
2012-05-01
影响因子：
6
通讯作者：
Chandran, Siddharthan
中科院分区：
文献类型：
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作者：
Hampton, David W.;Innes, Neill;Chandran, Siddharthan
年龄除了是神经退行性疾病的既定风险因素外，越来越多的人认识到年龄对再生有不利影响。越来越多的证据也表明，年龄在多发性硬化症的退行性和不可治疗的晚期中，在病程和预后方面发挥着重要的作用，尽管人们对此知之甚少。多发性硬化症的两个实验模型在模拟神经元损伤和再生的不同方面特别有影响：全局实验性自身免疫性脑脊髓炎和局部毒素介导的损伤。在此背景下，我们报告了一种免疫介导的脱髓鞘损伤的局灶性模型，该模型可靠地产生了靶向性的原发性脱髓鞘和轴突损伤。这一模型的详细病理特征从早期的研究中进行了广泛的修改，显示与年轻动物相比，老年成年动物对轴突损伤的易感性增加，重新髓鞘形成的效率降低。更重要的是，老年动物的再髓鞘形成主要是由雪旺细胞介导的，而在年轻啮齿动物中主要是由中枢少突胶质细胞介导的再髓鞘形成。总之，这些发现建立了一个实验平台，进一步研究年龄对人类脱髓鞘损伤生物相关模型中损伤和修复的影响。(Am J Pathol2012,18018971905；DOI：10.1016/j.ajpath.2012.01.018)
In addition to being an established risk factor for neurodegenerative diseases, age is increasingly recognized as adversely influencing regeneration. Accumulating evidence also suggests that age plays important, although poorly understood, roles with respect to course and prognosis in the degenerative and untreatable later phase of multiple sclerosis. Two experimental models of multiple sclerosis have been particularly influential in modeling the different aspects of neuronal injury and regeneration: global experimental autoimmune encephalomyelitis and focal toxin-mediated injury. Against this background, we report a focal model of immune-mediated demyelinating injury that reliably generates targeted primary demyelination and axonal injury. A detailed pathologic characterization of this model, modified extensively from an earlier study, showed that aged adult animals exhibited increased vulnerability to axonal injury and reduced efficiency of remyelination compared with younger animals. More important, remyelination in aged animals was predominantly Schwann cell mediated, in contrast to the central oligodendrocyte-mediated remyelination that predominated in younger rodents. Together, these findings establish an experimental platform to further study the influence of age on injury and repair in a biologically relevant model of human demyelinating injury. (Am J Pathol 2012, 180: 1897-1905; DOI: 10.1016/j.ajpath.2012.01.018)