A glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system.

Particularly, many neuro-developmental inhibitor molecules are secreted by the cells within the scar that prevent complete physical and functional recovery of the central nervous system after injury or disease.

[2] After injury, astrocytes undergo morphological changes, extend their processes, and increase synthesis of glial fibrillary acidic protein (GFAP).

GFAP is an important intermediate filament protein that allows the astrocytes to begin synthesizing more cytoskeletal supportive structures and extend pseudopodia.

Ultimately, the astrocytes form a dense web of their plasma membrane extensions that fills the empty space generated by the dead or dying neuronal cells (a process called astrogliosis).

The heavy proliferation of astrocytes also modifies the extracellular matrix surrounding the damaged region by secreting many molecules including laminin, fibronectin, tenascin C, and proteoglycans.

[10] The basal membrane is a histopathological extracellular matrix feature that forms at the center of injury and partially covers the astrocytic processes.

Ultimately, the astrocytes attach to the basal membrane, and the complex surrounds the blood vessels and nervous tissue to form the initial wound covering.

Moreover, the glial scar stimulates revascularization of blood capillaries to increase the nutritional, trophic, and metabolic support of the nervous tissue.

Following trauma to the CNS, axons begin to sprout and attempt to extend across the injury site in order to repair the damaged regions.

Two neuronally-important subclasses of transforming growth factor family of molecules are TGFβ-1 and TGFβ-2 that directly stimulate astrocytes, endothelial cells, and macrophages.

Particularly, interleukin-1, a protein produced by mononuclear phagocytes, helps to initiate the inflammatory response in astrocytes, leading to reactive astrogliosis and the formation of the glial scar.

IFNγ has been shown to induce astrocyte proliferation and increase the extent of glial scarring in injured brain models.

CNTF has been shown to promote the survival of neuronal cultures in vitro, and it can also act as a differentiator and trophic factor on glial cells.

However, Frisen et al. determined that nestin is also upregulated during severe stresses such as lesions which involve the formation of the glial scar.

[citation needed] Such proteins can increase astrocyte proliferation and can also lead to cell death, thus exacerbating cellular damage at the lesion site.

Moreover, reduced astrocyte proliferation decreases expression of chondroitin sulfate proteoglycans (CSPGs), major extracellular matrix molecules associated with inhibition of neuroregneration after trauma to the CNS.

One hour-post administration, olomoucine suppressed microglial proliferation, as well as reduced the tissue edema normally present during the early stages of glial scar formation.

[22] In 2004, Nikulina et al. showed that administration of rolipram, a PDE4 inhibitor, can increase cAMP levels in neurons after spinal cord injury.

10 day administration of rolipram in spinal cord injured rodents resulted in considerable axonal growth associated with a reduction in glial scarring at 2 weeks post-injury.

[25] As noted in the above section, transforming growth factor-β2 (TGFβ2) is an important glial scar stimulant that directly affects astrocyte proliferation.