Building a pathway to recovery: Targeting ECM remodeling in CNS injuries

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.