Chari Divya M, Zhao Chao, Kotter Mark R, Blakemore William F, Franklin Robin J M
Cambridge Centre for Brain Repair and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
J Neurosci Res. 2006 Mar;83(4):594-605. doi: 10.1002/jnr.20763.
High dose corticosteroid (CS) administration is a common mode of therapy in treatment of acute relapses in multiple sclerosis (MS) but the effects of CS on remyelination and the cellular mechanisms mediating this repair process are controversial. We have examined CS effects on repair of toxin-induced demyelinating lesions in the adult rat spinal cord. Corticosteroids reduced the extent of oligodendrocyte remyelination at 1 month post lesion (whereas Schwann-cell mediated repair was unaffected). However, CS did not cause permanent impairment of remyelination as lesions were fully remyelinated at 2 months after cessation of treatment. The delay in oligodendrocyte mediated repair could be attributed to inhibition of differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes, with no effect of CS treatment observed on OPC colonisation of the lesions. No differences were observed in animals treated with methylprednisolone succinate alone or with a subsequent prednisone taper indicating that CS effects occur at an early stage of repair. The potential consequences of delayed remyelination in inflammatory lesions are discussed.
高剂量皮质类固醇（CS）给药是治疗多发性硬化症（MS）急性复发的常见治疗方式，但CS对髓鞘再生的影响以及介导这一修复过程的细胞机制仍存在争议。我们研究了CS对成年大鼠脊髓毒素诱导的脱髓鞘损伤修复的影响。皮质类固醇在损伤后1个月时降低了少突胶质细胞髓鞘再生的程度（而雪旺细胞介导的修复未受影响）。然而，CS并未导致髓鞘再生的永久性损伤，因为在停止治疗2个月后损伤已完全髓鞘化。少突胶质细胞介导的修复延迟可能归因于少突胶质前体细胞（OPC）向少突胶质细胞分化的抑制，未观察到CS治疗对损伤部位OPC定植有影响。单独使用琥珀酸甲泼尼龙或随后逐渐减量使用泼尼松治疗的动物未观察到差异，表明CS的作用发生在修复的早期阶段。本文讨论了炎症性损伤中髓鞘再生延迟的潜在后果。
