Glial Scar Formation in CNS injury: A sub-map

Injury of body organs is usually accompanied by fibrosis that substantially affects regeneration of damaged tissue. Central nervous system (CNS) injuries including spinal cord injury (SCI) involve reactive gliosis and scarring.  SCI results in severe and irreversible loss of function. 

The role of the glial scar in CNS injuries remain complex. This is due to the dual contradictory beneficial and inhibitory roles on the axonal recovery and the various responses in different timings after the injury. For decades, the glial scar has been regarded as a physical and molecular barrier inhibiting axonal regrowth. This is supported by the production of scar forming-cells to the chondroitin sulfate proteoglycans (CSPGs) which are well-known extra-cellular components that inhibit axonal regeneration. More recently, the inhibition of glial scar formation in the acute and subacute stages after injury was found to prevent spontaneous recovery. This is due to the capability of the glial scar to limit the inflammatory mediators, thus prohibiting the spread of the debris to the healthy neural tissue. Extensive research is directed toward the manipulation of biomarkers and cells in the glial scars.

Mapping is a useful tool for data integration which allows researchers to visualize all the relative signaling, metabolic and omics pathways to the multi-etiological diseases. This helps generate ideas about gaps in knowledge and potential therapies. We designed a map illustrating pathophysiology of the glial scar formation in the CNS injury using CellDesigner 4.4.2 (Systems Biology Institute, Tokyo, Japan), as a part of a bigger SCI map. In the current map, we curated 129 reactions among 162 species with annotating of 85 PubMed-indexed references. We used HGNC, MeSH, Gene Ontology, InterPro, Ensembl and ChEBI for annotating different species.

Further, our map highlights the role of reactive astrocytes, scar-forming astrocytes, microglia, oligodendrocyte, ependymal cells pericytes, endothelial cells, macrophages, neutrophils, fibroblasts, stem cells in early endogenous repair, however later they form a glial scar that potentiates more damage. The map also shows the molecular pathways behind the cellular activation, including the role of STAT-3 signaling which is an essential modulator of reactive astrogliosis and scar-forming astrocytes.

Acknowledgement: We thank Luxembourg Centre for Systems Biomedicine (LCSB) for training us on cellDesigner software.