CNS Injury, Glial Scars, and Inflammation: Inhibitory extracellular matrices and regeneration failure

Spinal cord and brain injuries trigger complex interactions within the central nervous system as the body attempts to repair tissue damage. Glial cells, inflammation, and wound healing significantly impact the resulting disability. Neuronal regeneration after spinal cord injury is hindered by inflammatory cell activation, reactive astrogliosis, and the production of inhibitory extracellular molecules. Glial scars, once thought to be purely mechanical barriers, contain these inhibitory molecules. Unlike myelin-associated inhibitory molecules, inhibitory extracellular matrix molecules increase dramatically during the inflammatory stages post-injury, offering a window for therapeutic intervention. Modulating inflammation and altering the composition of inhibitory molecules could improve rehabilitation outcomes.

• 1
  Glial scars are not merely physical barriers but sources of inhibitory molecules that prevent successful regeneration after CNS injury.
• 2
  Inhibitory extracellular matrix molecules, such as proteoglycans, are upregulated in areas of gliosis following traumatic injuries and BBB breakdown, creating a non-permissive environment for axonal regeneration.
• 3
  Combination therapies involving modification of inflammatory states, neutralization of inhibitory extracellular molecules, and stimulation of growth-promoting factors show promise for improving rehabilitation after spinal injury.