Neonatal high pressure hydrocephalus is associated with elevation of pro-inflammatory cytokines IL-18 and IFNγ in cerebrospinal fluid

In neonatal HPHC (n = 30) and controls (n = 15), we compared CSF concentrations of IL18, IFNγ and sFasL using sandwich ELISA. HPHC was grouped according to etiology: spina bifida aperta (n = 20), aqueduct stenosis (n = 4), and fetal intra-cerebral haemorrhage (n = 6). Neonatal control CSF was derived from otherwise healthy neonates (n = 15), who underwent lumbar puncture for exclusion of meningitis.In all three HPHC groups, CSF IL18 concentrations were significantly higher than control values, and the fetal intracranial haemorrhage group was significantly higher than SBA group. Similarly, in all HPHC groups CSF-IFNγ concentrations significantly exceeded the control group. In both HPHC and control neonates, CSF FasL concentrations remained within the range of reference values.Independent of the pathogenesis, neonatal HPHC is associated with the activation of the pro-inflammatory cytokines (IL-18 and IFNγ) in the CSF, whereas CSF apoptosis biomarkers (sFasL) were unchanged. This suggests that anti-inflammatory treatment (in addition to shunting) could be helpful to preserve cerebral white matter.Since the introduction of innovative drainage valves and third ventricular endoscopy, neurosurgical treatment strategies for neonatal HPHC have improved. Nevertheless, HPHC is still associated with irreversible white matter damage and adverse neurological outcome [1-4]. After hypoxemia/ischemia, white matter damage consists of a diffuse, inflammatory pattern involving pro-inflammatory cytokines, oligodendrocytic injury, gliosis and myelin loss [5-7]. Pro-inflammatory cytokines are biologically active proteins produced by T cells, astrocytes and microglial cells. After cytokine release, immune cells invade the brain and subsequently activate astrocytes and microglial cells, which results in apoptosis and gliosis [5,8].Especially, the immature central nervous system is vulnerable for inflammatory damage. This is attributed to the specific sensitivity of immature oligodendrocytes