Nerve growth factor expression correlates with severity and outcome of traumatic brain injury in children.
BACKGROUND
Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms, mainly dependent on the intracerebral production of cytokines. In particular, interleukin 1beta (IL-1beta) 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.


OBJECTIVE
To determine whether the concentration of IL-1beta 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 2h (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-1beta 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-1beta 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-1beta expression, correlates with a favorable neurologic outcome. Clinical and prognostic information may also be obtained from IL-6 expression.
Chiaretti
Antonio
A
Paediatric Intensive Care Unit, Catholic University School of Medicine, Rome, Italy. achiaretti@yahoo.it
Antonelli
Alessia
A
Riccardi
Riccardo
R
Genovese
Orazio
O
Pezzotti
Patrizio
P
Di Rocco
Concezio
C
Tortorolo
Luca
L
Piedimonte
Giovanni
G
D000293:Adolescent; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001930:Brain Injuries / Q000134:cerebrospinal fluid*; D019208:Brain-Derived Neurotrophic Factor / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D005260:Female; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000134:cerebrospinal fluid; D006801:Humans; D007118:Immunoassay; D007223:Infant; D053583:Interleukin-1beta / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008297:Male; D020932:Nerve Growth Factor / Q000134:cerebrospinal fluid*; D020127:Recovery of Function
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D015850:Interleukin-6; D020932:Nerve Growth Factor