BACKGROUND:
In hydrocephalus an imbalance
between production and absorption of cerebrospinal fluid (CSF) results
in fluid accumulation, compression and stretching of the brain
parenchyma. In addition, changes in CSF composition have a profound
influence on the development and function of the brain and together,
these can result in severe life-long neurological deficits. Brain damage
or degenerative conditions can result in release of proteins expressed
predominantly in neurons, astroglia, or oligodendroglia into the brain
interstitial fluid, CSF and blood. Determination of such products in the
CSF might be of value in diagnosing cause, aetiology and/or assessing
the severity of the neurological damage in patients with hydrocephalus.
We therefore analysed CSF from human neonates with hydrocephalus for
these proteins to provide an insight into the pathophysiology associated
with different aetiologies.
METHODS:
CSF was collected
during routine lumbar puncture or ventricular tap. Samples were
categorized according to age of onset of hydrocephalus and presumed
cause (fetal-onset, late-onset, post-haemorrhagic or spina bifida
with hydrocephalus). Glial fibrillary acidic protein (GFAP), myelin
basic protein (MBP), vimentin and 2[prime], 3[prime]-cyclic nucleotide
3[prime]-phosphodiesterase (CNPase) were analysed through Western
blotting of hydrocephalic CSF samples (n = 17) and compared with data
from CSF of normal infants without neurological deficits (n = 8).
RESULTS:
GFAP
was significantly raised only in CSF from post-haemorrhagic
hydrocephalus while MBP was significantly raised in post-haemorrhagic
and in spina bifida
with hydrocephalus infants. Vimentin protein was only detected in some
CSF samples from infants with late-onset hydrocephalus but not from
other conditions. Surprisingly, CNPase was found in all neonatal CSF
samples, including normal and hydrocephalic groups, although it was
reduced in infants with late onset hydrocephalus compared with normal
and other hydrocephalic groups.
CONCLUSIONS:
Apart from
CNPase, which is an enzyme, the markers investigated are intracellular
intermediate filaments and would be present in CSF only if the cells are
compromised and the proteins released. Raised GFAP observed in
post-haemorrhagic hydrocephalus must reflect damage to astrocytes and
ependyma. Raised MBP in post-haemorrhagic and spina bifida
with hydrocephalus indicates damage to oligodendrocytes and myelin.
Vimentin protein detected in some of the late-onset hydrocephalic
samples indicates damage to glial and other progenitors and suggests
this condition affects periventricular regions. The presence of CNPase
in all CSF samples was unexpected and indicates a possible novel role
for this enzyme in brain development/myelination. Less CNPase in some
cases of late-onset hydrocephalus could therefore indicate changes in
myelination in these infants. This study demonstrates differential glial
damage and loss in the developing human neonatal hydrocephalic brain
associated with different aetiologies.
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