| |
 |
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.
|
|
|