Chronic spinal cord injury: physical and chemical barriers to axon regrowth1-5
The response of glial cells to the initial injury results in loss of white matter and the formation of a glial scar. A combination of mechanical blockage by the glial scar as well as the preponderance of inflammatory and inhibitory chemical signals prevent regrowth of severed axons. The degree to which surviving white matter is spared during these processes can determine the degree of eventual functional recovery. Being able to bypass the injured area and inhibitory milieu can offer opportunity for axon regeneration and functional recovery.
Reactive gliosis and the glial scar1,2
- In response to the mechanical injury, glial cells called astrocytes migrate to the site of the injury and attempt to repair damage, resulting in a reactive cascade that leads to the formation of a glial scar.
- The glial scar prevents neuronal processes from crossing the site of the lesion and making functional connections on the other side of the injury, acting both as a chemical barrier and physical barrier.
- The chemical barrier is due to the production of inhibitory molecules (eg, chondroitin sulphate proteoglycans [CSPGs] and keratan sulphate proteoglycans [KSPGs]) by reactive astrocytes in the glial scar.
- Inflammatory and ischemic changes at the site of the injury continue to cause progressive scarring and eventual cavitation.
- Surviving axons are capable of regenerative sprouting, but these efforts are inhibited both by factors at the site as well as the physical barrier created by scar and cyst formation.