In the presence of danger: The extracellular matrix defensive response to central nervous system injury

Neural Regen Res. 2014 Feb 15;9(4):377-384. doi: 10.4103/1673-5374.128238.


Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient neurotransmission and axon potential propagation. In the normal adult CNS the extracellular matrix (ECM) is relatively stable except in select regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review will highlight structural and functional features of the normal adult CNS ECM and then focus on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed.

Keywords: astrocyte; axon growth; contusion; glial scar; inflammation; inhibitory; macrophage; proteoglycan; regeneration; spinal cord injury.