The Role of Glial "scar" Formation on Outcome

A microglial cell from the cerebral cortex of a rat with congenital hydrocephalus. These cells have small cell bodies (arrow)and elaborate processes (arrow head) that react to brain lesions. These cells may form permanent "scars" throughout the hydrocephalic brain.
One of the major gaps in our understanding of the way hydrocephalus damages the brain involves how "scars" are formed within brain tissue and how they influence brain function. Neurosurgeons and engineers alike constantly strive to develop better drainage systems for hydrocephalic patients.

Nevertheless, their expertise is severely limited by the lack of data on how the mechanical properties of the brain, i.e. elasticity or compliance, stiffness or resistance, is changed by hydrocephalus. In hydrocephalus, scar formation is known to occur, but the time course and permanence of the reaction is not known.

Scar formation could play a major role in creating the problems that chronically plague hydrocephalic children. It has been suggested by many investigators, including ourselves, that scar formation is a permanent fixture in hydrocephalic brains, even those that have been shunted successfully.

Northern blot showing the amount of RNA for glial fibrillary acidic protein (GFAP), a marker for activated astrocytes. Astrocytes are non-neuronal cells that normally help nourish the brain, but during injury they grow and proliferate. GFAP levels in this hydrocephalic brain are higher than in the control brain, indicating that damage has occurred.
It is possible that scar formation may dramatically change the mechanical properties of the brain so that it becomes more resistant to increases in CSF pressure. Unfortunately, a more resistant hydrocephalic brain is more vulnerable to pressure changes, which occur with nearly every shunt malfunction. Furthermore, resistance has a direct effect on the way a shunt functions. Therefore, progress in shunt design has been hampered by the lack of information about the relationship between resistance and scar formation.
Our studies will determine for the first time when and how scars form in hydrocephalic brains, and whether their formation can be prevented or inhibited. Comprehensive analyses of both experimental models and patients will identify the cells that are responsible for scar formation, the impact of scar formation on brain function, better ways to diagnose scar formation, and novel treatments that block scar formation.

Recent advances in neurobiology have raised the possibility of preventing or minimizing scar formation. While these promising applications could theoretically supplement shunt treatments for hydrocephalus, their potential has never been tested.