Abstract

BackgroundIn 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.MethodsCSF 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′ , 3′-cyclic nucleotide 3′-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).ResultsGFAP 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.ConclusionsApart 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.

Highlights

  • In hydrocephalus an imbalance between production and absorption of cerebrospinal fluid (CSF) results in fluid accumulation, compression and stretching of the brain parenchyma

  • Raised Glial fibrillary acidic protein (GFAP) observed in post-haemorrhagic hydrocephalus must reflect damage to astrocytes and ependyma

  • Glial fibrillary acidic protein (GFAP) A 53 KDa, GFAP-positive protein band present in the CSF from Post-haemorrhagic hydrocephalus (PHH) and Spina bifida with hydrocephalus (SB/HC) infants was not detected in normal, Fetal-onset or congenital hydrocephalus (FOH) and Late-onset hydrocephalus (LOH) samples (Figure 1a)

Read more

Summary

Introduction

In hydrocephalus an imbalance between production and absorption of cerebrospinal fluid (CSF) results in fluid accumulation, compression and stretching of the brain parenchyma. 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. Surgery does address the life-threatening raised intracranial pressure, compression and stretching of the brain parenchyma, it does not recover lost or abnormal development, cellular damage or the life-long neurological issues resulting from these [4,5,6]

Objectives
Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call