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NGF, DCX, and NSE upregulation correlates with severity and outcome of head trauma in children

From the Pediatric Intensive Care Unit (A.C., A.A., O.G., L.T., G.C.) and Pediatric Oncology (G.B., R.R.), Catholic University Medical School; and Agency for Public Health of Lazio Region (P.P.), Rome, Italy.

Address correspondence and reprint requests to Dr. Antonio Chiaretti, Terapia Intensiva Pediatrica, Policlinico Gemelli, Largo Gemelli, 1-00168 Rome, Italy achiaretti{at}yahoo.it

Background: Secondary brain damage after traumatic brain injury (TBI) involves neuroinflammatory mechanisms, mainly dependent on the intracerebral production of specific biomarkers, such as cytokines, neurotrophic factors, and neuron-specific enolase (NSE). NSE is associated with neuronal damage, while neurotrophic factors play a neuroprotective role due to their ability to modulate neuronal precursor biosynthesis, such as doublecortin (DCX). However, the relationships between the expression of these factors and the severity and outcome of TBI are not understood.

Methods: To determine whether the concentrations of neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]), DCX, and NSE in the CSF of children with TBI correlate with the severity of brain damage and neurologic outcome, we prospectively collected CSF samples from 32 children at 2 and 48 hours after admission for severe TBI and from 32 matched controls. Severity of TBI was evaluated by Glasgow Coma Scale and neurologic outcome by Glasgow Outcome Score.

Results: Early NGF, DCX, and NSE concentrations correlated significantly with the severity of head injury, whereas no correlation was found for BDNF and GDNF. Furthermore, NGF and DCX upregulation and lower NSE expression were associated with better neurologic outcomes. No significant association was found between BDNF and GDNF expression and outcome.

Conclusions: Nerve growth factor (NGF), doublecortin (DCX), and neuron-specific enolase concentrations in the CSF are useful markers of brain damage following severe traumatic brain injury (TBI). NGF and DCX upregulation correlates also with better neurologic outcome and could be useful to obtain clinical and prognostic information in children with severe TBI.

Abbreviations: BDNF = brain-derived neurotrophic factor; DCX = doublecortin; FIM = Functional Independence Measures; GCS = Glasgow Coma Scale; GDNF = glial-derived neurotrophic factor; GOS = Glasgow Outcome Score; NGF = nerve growth factor; NSE = neuron-specific enolase; PICU = pediatric intensive care unit; SGZ = subgranular zone; SVZ = subventricular zone; TBI = traumatic brain injury.

Supplemental data at www.neurology.org

Disclosure: The authors report no disclosures.

Received June 17, 2008. Accepted in final form November 6, 2008.