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Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: inflammatory cytokines

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Abstract

Purpose

Hydrocephalus (HC) has a multifactorial and complex picture of pathophysiology due to aetiology, age at and duration since onset. We have previously identified distinctions in markers of cell death associated with different aetiologies. Here, we examined cerebrospinal fluid (CSF) from human HC neonates for cytokines to identify further distinguishing features of different aetiologies.

Methods

CSF was collected during routine lumbar puncture or ventricular tap from neonates with hydrocephalus, or with no neurological condition (normal controls). Total protein, Fas receptor, Fas ligand, stem cell factor (SCF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin growth factor-1 (IGF-1), tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured and compared between 8 unaffected and 28 HC neonatal CSF samples.

Results

Total protein was significantly (P < 0.05) raised in late-onset hydrocephalus (LOH). Fas receptor was raised (P < 0.05) in post-haemorrhagic hydrocephalus (PHH) and spina bifida with hydrocephalus (SB/HC), but no difference in Fas ligand was found. SCF was raised (P < 0.05) in SB/HC. HGF was found in all HC and was increased (P < 0.01) in PHH. Increased VEGF was found in PHH (P < 0.01) and SB/HC (P < 0.05). Variable levels of IL-6, TNF-α and IGF-1 were found in all HC groups compared with none in normal.

Conclusions

LOH was unusual with significantly raised total protein indicating an inflammatory state. Increased Fas receptor, VEGF, IGF-1 and HGF suggest anti-apoptotic and repair mechanism activation. By contrast, elevated TNF-α and IL-6 indicate inflammatory processes in these neonatal brains. Taken with our previous study, these data indicate that different pathophysiology, inflammation and repair are occurring in HC of different aetiologies and that additional treatment strategies may benefit these infants in addition to fluid diversion.

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Acknowledgments

Financial support was provided by The Charles Wolfson Charitable Trust (JAM). Miss Naureen was supported through a British Council INSPIRE grant (SP055) to The University of Manchester, UK and COMSATS Institute for Information Technology, Islamabad, Pakistan that also supported the work carried out in Islamabad and Lahore. We thank Dr. Nadeem Malik (neurosurgeon) and the Neonatology registrars at the Children’s Hospital Lahore for CSF collections in Pakistan; Sasha Burn, Dawn Williams, Clare Jennings, Anna Hendrickson and Jennifer Hill for CSF collections in the UK; Professor M. Akhtar, FRS and Dr Naeem of the School of Biological Sciences, University of Punjab, Lahore for access to laboratory facilities for sample preparation and lyophilisation.

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Authors and Affiliations

  1. Faculty of Life Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

    Irum Naureen & Jaleel A. Miyan

  2. Department of Neonatology, The Children’s Hospital and Institute of Child Health, Ferozepur Road, Lahore, Pakistan

    Kh. A. Irfan Waheed & Ahsen W. Rathore

  3. Institute of Human Development, Manchester Academic Health Sciences Centre, The University of Manchester, Oxford Road, Manchester, M13 9WL, UK

    Suresh Victor

  4. Neurosurgical Unit, Alder Hey Children’s Hospital, Eaton Road, Liverpool, L12 2AP, UK

    Conor Mallucci

  5. Department of Neurosurgery, Leeds General Infirmary, Great George Street, Leeds, LS1 3EX, UK

    John R. Goodden

  6. Department of Biosciences, COMSATS Institute of Information and Technology, Islamabad, Pakistan

    Irum Naureen & Shahid N Chohan

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  1. Irum Naureen
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Naureen, I., Waheed, K.A.I., Rathore, A.W. et al. Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: inflammatory cytokines. Childs Nerv Syst 30, 1155–1164 (2014). https://doi.org/10.1007/s00381-014-2415-6

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