Current Advancements in Spinal Cord Injury Research-Glial Scar Formation and Neural Regeneration

Abstract

Spinal cord injury (SCI) is a complex tissue injury resulting in permanent and degenerating damage to the central nervous system (CNS). Detrimental cellular processes occur after SCI, including axonal degeneration, neuronal loss, neuroinflammation, reactive gliosis, and scar formation. The glial scar border forms to segregate the neural lesion and isolate spreading inflammation, reactive oxygen species, and excitotoxicity at the injury epicenter to preserve surrounding healthy tissue. The scar border is a physicochemical barrier composed of elongated astrocytes, fibroblasts, and microglia secreting chondroitin sulfate proteoglycans, collogen, and the dense extra-cellular matrix. While this physiological response preserves viable neural tissue, it is also detrimental to regeneration. To overcome negative outcomes associated with scar formation, therapeutic strategies have been developed: the prevention of scar formation, the resolution of the developed scar, cell transplantation into the lesion, and endogenous cell reprogramming. This review focuses on cellular/molecular aspects of glial scar formation, and discusses advantages and disadvantages of strategies to promote regeneration after SCI.

Keywords: cell reprogramming; cell transplantation; glial scar formation; neural regeneration; neural stem progenitor cells; spinal cord; therapy; traumatic injury.

Figure 1

Schematic diagram illustrating glial scar formation. (A) Formation of the lesion and scar during the acute phase of SCI. (B) Formation of the fibrotic tissue and glial scar during the chronic phase of SCI. (C) White box region in B detailing the layers of the glial scar: I. astrocytes, II. microglia, III. secreted stromal ECM/CSPGs, IV. fibroblasts, and V. stromal ECM/CSPGs and penetrating macrophages.

Figure 2

Current research in therapeutic interventions. Current cellular and molecular strategies to treat SCI include (A) therapeutics targeting the glial scar, (B) cell transplantation, and (C) endogenous cell reprogramming. These strategies each have their own pros and cons, with new genetic and biotechnological advances regularly changing the landscape of each type. Advances in each field over the last 5–10 years are highlighted in the following sections.