The extracellular matrix (ECM) provides protection, rigidity, and structure toward cells. It consists, among others, of a wide variety of glycoproteins and proteoglycans, which act together to produce a complex and dynamic environment, most relevant in transmembrane events. In the brain, the ECM occupies a notable proportion of its volume and maintains the homeostasis of central nervous system (CNS). In addition, remodeling of the ECM, that is transient changes in ECM proteins regulated by matrix metalloproteinases (MMPs), is an important process that modulates cell behavior upon injury, thereby facilitating recovery. Failure of ECM remodeling plays an important role in the pathogenesis of multiple sclerosis (MS), a neurodegenerative demyelinating disease of the CNS with an inflammatory response against protective myelin sheaths that surround axons. Remyelination of denuded axons improves the neuropathological conditions of MS, but this regeneration process fails over time, leading to chronic disease progression. In this review, we uncover abnormal ECM remodeling in MS lesions by discussing ECM remodeling in experimental demyelination models, that is when remyelination is successful, and compare alterations in ECM components to the ECM composition and MMP expression in the parenchyma of demyelinated MS lesions, that is when remyelination fails. Inter- and intralesional differences in ECM remodeling in the distinct white matter MS lesions are discussed in terms of consequences for oligodendrocyte behavior and remyelination (failure). Hence, the review will aid to understand how abnormal ECM remodeling contributes to remyelination failure in MS lesions and assists in developing therapeutic strategies to promote remyelination.

中文翻译：

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白质多发性硬化病变中间质细胞外基质的重塑：对髓鞘再生（失败）的影响。

细胞外基质 (ECM) 为细胞提供保护、刚性和结构。它由多种糖蛋白和蛋白聚糖组成，它们共同作用以产生复杂和动态的环境，与跨膜事件最相关。在大脑中，ECM 占据其体积的显着比例并维持中枢神经系统 (CNS) 的稳态。此外，ECM 的重塑，即由基质金属蛋白酶 (MMP) 调节的 ECM 蛋白的瞬时变化，是调节损伤后细胞行为的重要过程，从而促进恢复。ECM 重构失败在多发性硬化症 (MS) 的发病机制中起着重要作用，一种中枢神经系统的神经退行性脱髓鞘疾病，对围绕轴突的保护性髓鞘产生炎症反应。裸露轴突的髓鞘再生改善了 MS 的神经病理状况，但这种再生过程会随着时间的推移而失败，导致慢性疾病进展。在这篇综述中，我们通过讨论实验性脱髓鞘模型中的 ECM 重构（即髓鞘再生成功时）来揭示 MS 病变中异常的 ECM 重构，并将 ECM 成分的改变与脱髓鞘 MS 病变实质中的 ECM 组成和 MMP 表达进行比较，即是髓鞘再生失败的时候。根据少突胶质细胞行为和髓鞘再生（失败）的后果讨论了不同白质 MS 病变中 ECM 重塑的病灶间和病灶内差异。因此，