Nerve growth factor expression correlates with severity and outcome of traumatic brain injury in children

Abstract

Background Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms, mainly dependent on the intracerebral production of cytokines. In particular, interleukin 1β (IL-1β) is associated with neuronal damage, while interleukin 6 (IL-6) exerts a neuroprotective role due to its ability to modulate neurotrophins biosynthesis. However, the relationship between these cytokines and neurotrophins with the severity and outcome of TBI remains still controversial. Aims To determine whether the concentration of IL-1β and IL-6 and neurotrophins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF)) in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and its neurologic outcome. Methods Prospective observational clinical study in a university hospital. CSF samples were collected from 27 children at 2 h (Time T1) and 48 h (Time T2) after severe TBI, and from 21 matched controls. Severity of TBI was evaluated by GCS and neurologic outcome by GOS. CSF concentrations of cytokines and neurotrophins were measured by immunoenzymatic assays. Results Early NGF and IL-1β concentrations (T1) correlated significantly with the severity of head injury, whereas no correlation was found for IL-6, BDNF, and GDNF. Furthermore, higher NGF and IL-6 and lower IL-1β expression at T2 were associated with better neurologic outcomes. No significant association was found between BDNF or GDNF expression and neurologic outcome. Conclusions NGF concentration in CSF is a useful marker of brain damage following severe TBI and its up-regulation, in the first 48 h after head injury together with lower IL-1β expression, correlates with a favorable neurologic outcome. Clinical and prognostic information may also be obtained from IL-6 expression.