Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: glial proteins associated with cell damage and loss

Fluids and Barriers of the CNS

Jaleel A Miyan⁶  Shahid N Chohan³  John R Goodden¹  Conor Mallucci⁴  Suresh Victor⁵  Ahsen W Rathore²  Khawaja A Irfan Waheed²  Irum Naureen³ 

[1] Department of Neurosurgery, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK;Department of Neonatology, The Children’s Hospital and Institute of Child Health, Ferozepur Road, Lahore, Pakistan;Department of Biosciences, COMSATS Institute of Information and Technology, Islamabad, Pakistan;Neurosurgical Unit, Alder Hey Children’s Hospital, Eaton Road, Liverpool L12 2AP, UK;Institute of Human Development, Manchester Academic Health Sciences Centre, The University of Manchester, Oxford Road, Manchester M13 9WL, UK;Faculty of Life Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, UK

关键词: MBP;    CNPase;    Vimentin;    GFAP;    CSF;    Human neonates;    Hydrocephalus;   

Others  :  806289
DOI  :  10.1186/2045-8118-10-34

 received in 2013-09-02, accepted in 2013-12-14,  发布年份 2013

【 摘 要 】

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^′ , 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).

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.

【 授权许可】

   
2013 Naureen et al.; licensee BioMed Central Ltd.

【 图 表 】

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