Fibrotic Scar in CNS Injuries: From the Cellular Origins of Fibroblasts to the Molecular Processes of Fibrotic Scar Formation

Abstract

Central nervous system (CNS) trauma activates a persistent repair response that leads to fibrotic scar formation within the lesion. This scarring is similar to other organ fibrosis in many ways; however, the unique features of the CNS differentiate it from other organs. In this review, we discuss fibrotic scar formation in CNS trauma, including the cellular origins of fibroblasts, the mechanism of fibrotic scar formation following an injury, as well as the implication of the fibrotic scar in CNS tissue remodeling and regeneration. While discussing the shared features of CNS fibrotic scar and fibrosis outside the CNS, we highlight their differences and discuss therapeutic targets that may enhance regeneration in the CNS.

CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding

“…Central nervous system (CNS) trauma generates cellular debris, activates resident cells, infiltrates circulating immune cells, and eventually forms two distinct scars: glial scar and fibrotic scar [ 319 , 320 ]. As a unique form in CNS, glial scar is mainly formed by the accumulation of reactive astrocytes in injured sites [ 320 ].…”

“…Central nervous system (CNS) trauma generates cellular debris, activates resident cells, infiltrates circulating immune cells, and eventually forms two distinct scars: glial scar and fibrotic scar [ 319 , 320 ]. As a unique form in CNS, glial scar is mainly formed by the accumulation of reactive astrocytes in injured sites [ 320 ]. Reactive astrocytes, characterized by the increased expression of glial fibrillary acidic protein, surround the lesion and separate the injured area from normal tissue [ 320 , 321 ].…”

“…As a unique form in CNS, glial scar is mainly formed by the accumulation of reactive astrocytes in injured sites [ 320 ]. Reactive astrocytes, characterized by the increased expression of glial fibrillary acidic protein, surround the lesion and separate the injured area from normal tissue [ 320 , 321 ]. Fibrotic scar, located in the injured core, is characterized by the presence of fibroblasts and ECM deposition [ 320 ].…”

“…Reactive astrocytes, characterized by the increased expression of glial fibrillary acidic protein, surround the lesion and separate the injured area from normal tissue [ 320 , 321 ]. Fibrotic scar, located in the injured core, is characterized by the presence of fibroblasts and ECM deposition [ 320 ]. Although the similar of CNS fibrotic scar to other organ fibrosis, its formation process may be quite different due to the unique CNS environment [ 320 ].…”

“…Fibrotic scar, located in the injured core, is characterized by the presence of fibroblasts and ECM deposition [ 320 ]. Although the similar of CNS fibrotic scar to other organ fibrosis, its formation process may be quite different due to the unique CNS environment [ 320 ]. Various cell types in CNS such as fibroblasts, astrocytes, microglia, pericytes, and endothelial cells play important roles in formation of fibrotic scar [ 320 ].…”