Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India.
Brain Res. 2023 Nov 15;1819:148533. doi: 10.1016/j.brainres.2023.148533. Epub 2023 Aug 14.
Extracellular matrix (ECM) is a complex and dynamic network of proteoglycans, proteins, and other macromolecules that surrounds cells in tissues. The ECM provides structural support to cells and plays a critical role in regulating various cellular functions. ECM remodeling is a dynamic process involving the breakdown and reconstruction of the ECM. This process occurs naturally during tissue growth, wound healing, and tissue repair. However, in the context of central nervous system (CNS) injuries, dysregulated ECM remodeling can lead to the formation of fibrotic and glial scars. CNS injuries encompass various traumatic events, including concussions and fractures. Following CNS trauma, the formation of glial and fibrotic scars becomes prominent. Glial scars primarily consist of reactive astrocytes, while fibrotic scars are characterized by an abundance of ECM proteins. ECM remodeling plays a pivotal and tightly regulated role in the development of these scars after spinal cord and brain injuries. Various factors like ECM components, ECM remodeling enzymes, cell surface receptors of ECM molecules, and downstream pathways of ECM molecules are responsible for the remodeling of the ECM. The aim of this review article is to explore the changes in ECM during normal physiological conditions and following CNS injuries. Additionally, we discuss various approaches that target various factors responsible for ECM remodeling, with a focus on promoting axon regeneration and functional recovery after CNS injuries. By targeting ECM remodeling, it may be possible to enhance axonal regeneration and facilitate functional recovery after CNS injuries.
细胞外基质(ECM)是一种复杂而动态的蛋白聚糖、蛋白质和其他大分子网络,围绕着组织中的细胞。ECM 为细胞提供结构支持,并在调节各种细胞功能方面起着关键作用。ECM 重塑是一个涉及 ECM 分解和重建的动态过程。这个过程在组织生长、伤口愈合和组织修复过程中自然发生。然而,在中枢神经系统(CNS)损伤的情况下,失调的 ECM 重塑会导致纤维性和神经胶质瘢痕的形成。CNS 损伤包括各种创伤性事件,如脑震荡和骨折。CNS 损伤后,神经胶质和纤维性瘢痕的形成变得明显。神经胶质瘢痕主要由反应性星形胶质细胞组成,而纤维性瘢痕的特征是 ECM 蛋白的大量存在。ECM 重塑在脊髓和脑损伤后这些瘢痕的形成中起着关键和严格调节的作用。各种因素,如 ECM 成分、ECM 重塑酶、ECM 分子的细胞表面受体以及 ECM 分子的下游途径,都负责 ECM 的重塑。本文综述的目的是探讨 ECM 在正常生理条件下和中枢神经系统损伤后的变化。此外,我们还讨论了针对各种负责 ECM 重塑的因素的各种方法,重点是促进 CNS 损伤后的轴突再生和功能恢复。通过靶向 ECM 重塑,可能增强轴突再生并促进 CNS 损伤后的功能恢复。