title: Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: inflammatory cytokines.
abstract: OBJECTIVE
  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.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Irum
authors.initials: I
authors.lastname: Naureen
authors.forename: Kh A Irfan
authors.initials: KhA
authors.lastname: Waheed
authors.forename: Ahsen W
authors.initials: AW
authors.lastname: Rathore
authors.forename: Suresh
authors.initials: S
authors.lastname: Victor
authors.forename: Conor
authors.initials: C
authors.lastname: Mallucci
authors.forename: John R
authors.initials: JR
authors.lastname: Goodden
authors.forename: Shahid N
authors.initials: SN
authors.lastname: Chohan
authors.forename: Jaleel A
authors.initials: JA
authors.lastname: Miyan
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000134:cerebrospinal fluid* / Q000209:etiology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male
chemical_list: D015415:Biomarkers
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