http://www.sciencedirect.com/science...fddb87ac1b8823
CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Michael T. Fitcha and Jerry Silverb
Department of Emergency Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA

Received 15 May 2007; accepted 22 May 2007. Available online 31 May 2007.




Abstract

Spinal cord and brain injuries lead to complex cellular and molecular interactions within the central nervous system in an attempt to repair the initial tissue damage. Many studies have illustrated the importance of the glial cell response to injury, and the influences of inflammation and wound healing processes on the overall morbidity and permanent disability that result. The abortive attempts of neuronal regeneration after spinal cord injury are influenced by inflammatory cell activation, reactive astrogliosis and the production of both growth promoting and inhibitory extracellular molecules. Despite the historical perspective that the glial scar was a mechanical barrier to regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Unlike myelin associated inhibitory molecules, which remain at largely static levels before and after central nervous system trauma, inhibitory extracellular matrix molecules are dramatically upregulated during the inflammatory stages after injury providing a window of opportunity for the delivery of candidate therapeutic interventions. While high dose methylprednisolone steroid therapy alone has not proved to be the solution to this difficult clinical problem, other strategies for modulating inflammation and changing the make up of inhibitory molecules in the extracellular matrix are providing robust evidence that rehabilitation after spinal cord and brain injury has the potential to significantly change the outcome for what was once thought to be permanent disability.

Keywords: Astrocytes; Glial scar; Spinal injury; Regeneration; Inflammation; Proteoglycan; Extracellular matrix



Corresponding author. Fax: +1 336 716 5438.