Nerve growth factor and doublecortin expression correlates with improved outcome in children with severe traumatic brain injury.
BACKGROUND
In the adult brain, migrating neuroblasts can replace damaged neurons after severe traumatic brain injury (TBI). Little is known about which factors determine the magnitude and amplification of neurogenesis after TBI, but there are some evidences that the nerve growth factor (NGF) and the doublecortin (DCX) can influence neurogenesis and neuronal repair.


METHODS
This study investigates the NGF and DCX levels in the cerebrospinal fluid of 12 children with severe TBI and 12 matched controls, to determine the correlation between the expression of both these factors and the patients outcome. We collected cerebrospinal fluid samples 2 hours (Time T1) and 48 hours (Time T2) after brain injury. NGF levels were measured using a two-site immunoenzymatic assay, whereas the DCX expression by a Western blot analysis.


RESULTS
At time T1 and T2, children with the best outcomes had higher levels of NGF than children with poor outcomes. Evaluating the change of NGF levels from time T1 to time T2, we found that the NGF up-regulation in the early time after injury was significantly associated with good outcomes of patients. Concomitantly, the expression of DCX increased only in patients with NGF up-regulation from time T1 to time T2. In others patients and in controls the expression of DCX remained unchanged.


CONCLUSIONS
Based on these results, we hypothesize that NGF and DCX contribute to the mechanisms of neuroprotection and neuronal connection reorganization after TBI, playing a key role in the outcome of these patients.
Chiaretti
Antonio
A
Pediatric Intensive Care Unit, Catholic University Medical School, Rome, Italy.
Antonelli
Alessia
A
Genovese
Orazio
O
Pezzotti
Patrizio
P
Rocco
Concezio Di
CD
Viola
Luigi
L
Riccardi
Riccardo
R
D000293:Adolescent; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000628:therapy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003422:Critical Care; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000134:cerebrospinal fluid*; D020932:Nerve Growth Factor / Q000134:cerebrospinal fluid*; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D015599:Trauma Severity Indices; D016896:Treatment Outcome
C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D020932:Nerve Growth Factor