Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Gang Chen,Yujuan Dai,Tuo Yang,Shusen Cui

doi:10.3389/fncel.2020.00078

Abstract

Recovery from spinal cord injury (SCI) remains an unsolved problem. As a major component of the SCI lesion, the glial scar is primarily composed of scar-forming astrocytes and plays a crucial role in spinal cord regeneration. In recent years, it has become increasingly accepted that the glial scar plays a dual role in SCI recovery. However, the underlying mechanisms of this dual role are complex and need further clarification. This dual role also makes it difficult to manipulate the glial scar for therapeutic purposes. Here, we briefly discuss glial scar formation and some representative components associated with scar-forming astrocytes. Then, we analyze the dual role of the glial scar in a dynamic perspective with special attention to scar-forming astrocytes to explore the underlying mechanisms of this dual role. Finally, taking the dual role of the glial scar into account, we provide several pieces of advice on novel therapeutic strategies targeting the glial scar and scar-forming astrocytes.

Highlights

The past decades have witnessed a rapid increase in studies on the pathology and molecular mechanisms of and therapeutic strategies for spinal cord injury (SCI)
M2 macrophage-stimulated astrocytes can inhibit the proliferation of both M1 and M2 macrophages and decrease the production of proinflammatory factors (Haan et al, 2015). All of these results indicate that macrophages have a critical influence on glial scar formation and scar-forming astrocytes
According to the timeline of SCI development and glial scar formation, we summarize the dual role of the glial scar (Figure 1)

Summary

INTRODUCTION

The past decades have witnessed a rapid increase in studies on the pathology and molecular mechanisms of and therapeutic strategies for spinal cord injury (SCI). NG2-OPCs can differentiate into astrocytes in injured CNS including in SCI (Raff et al, 1983; Sellers et al., 2009; Hackett et al, 2016) This differentiation of NG2-OPCs into astrocytes is mainly induced by the expression of bone morphogenetic proteins (BMPs) by reactive astrocytes, contributing to glial scar formation (Wang et al, 2011). Scar-Forming Astrocytes Are Major, but Not Predominant, Producers of CSPGs Another reason why the glial scar was previously considered a crucial inhibitor is that the glial scar participates in building an inhibitory ECM for axonal regeneration by permanently producing several inhibitory molecules, including CSPGs. Astrocytes express increased levels of CSPGs after SCI and were previously thought to be the predominant producers of CSPGs (McKeon et al, 1999; Jones et al, 2003). Ablation of reactive astrocytes by the HSV-TK/GCV system shRNA-mediated PTEN suppression

Results

SUMMARY AND RECOMMENDATIONS FOR FUTURE STUDY

CONCLUSIONS