ABSTRACT: 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.
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.
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.
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.
The Journal of trauma 08/2008; 65(1):80-5. · 2.48 Impact Factor
ABSTRACT: 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.
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.
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.
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.
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.
European Journal of Paediatric Neurology 06/2008; 12(3):195-204. · 2.12 Impact Factor
ABSTRACT: Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms that are mainly dependent on the intracerebral production of cytokines. Interleukin-6 (IL-6) may have a role both in the pathogenesis of neuronal damage and in the recovery mechanisms of injured neurons through the modulation of nerve growth factor (NGF) biosynthesis. However, the relationship between IL-6 and NGF expression and the severity and outcome of TBI remains controversial. We have conducted a prospective observational clinical study to determine whether the concentration of IL-6 and NGF in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and neurologic outcome of patients. CSF samples were collected from 29 children at 2 h (time T1) and 48 h (time T2) after severe TBI, and from 31 matched controls. TBI severity was evaluated by Glasgow Coma Scale (GCS) and neurologic outcome by Glasgow Outcome Score (GOS). CSF concentrations of IL-6 and NGF were measured by immunoenzymatic assays. Early NGF concentrations (T1) correlated significantly with head injury severity, whereas no correlation was found between GCS and IL-6. Furthermore, IL-6 and NGF upregulation after injury was associated with better neurologic outcomes. Based on these findings, we posit that NGF expression is a useful marker of brain damage following severe TBI. Moreover, the early upregulation of both IL-6 and NGF, which correlates with a favorable neurologic outcome, may reflect an endogenous attempt at neuroprotection in response to the damaging biochemical and molecular cascades triggered by traumatic insult.
Journal of Neurotrauma 04/2008; 25(3):225-34. · 3.65 Impact Factor