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

Objective Traumatic brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms, mainly dependent on the intracerebral production of cytokines. IL-1β is associated with neuronal damage, whereas IL-6 exerts a neuroprotective role due to its ability to modulate neurotrophin biosynthesis. However, the relationship between these cytokines and neurotrophins with the severity and outcome of TBI still remains controversial. 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 neurological 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. The severity of TBI was evaluated by Glasgow coma scale and neurological outcome by the Glasgow outcome scale. 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 neurological outcomes. No significant association was found between BDNF or GDNF expression and neurological outcome. Conclusions NGF concentration in CSF is a useful marker of brain damage following severe TBI and its regulation, in the first 48 h after head injury together with lower IL-1β expression, correlates with a favourable neurological outcome. Clinical and prognostic information may also be obtained from IL-6 expression.