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Correlation between neurotrophic factor expression and outcome of children with severe traumatic brain injury
Antonio Chiaretti1, Marco Piastra, Giancarlo Polidori
1Pediatric Intensive Care Unit, Catholic University Medical School, Policlinico Gemelli, Largo Gemelli, 1-00168, Rome, Italy. achiaretti@yahoo.it
Insights
Neurotrophic factors like brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are altered after pediatric traumatic brain injury. NGF in cerebrospinal fluid may indicate a good outcome in children with severe head injuries.
Area of Science:
- Neuroscience
- Biochemistry
- Pediatric Critical Care
Background:
- Traumatic brain injury (TBI) in children can lead to complex biochemical changes.
- Neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glia-derived neurotrophic factor (GDNF), play crucial roles in neuronal survival and repair.
- Understanding their expression patterns post-TBI is vital for assessing injury severity and predicting outcomes.
Purpose of the Study:
- To evaluate the expression of NGF, BDNF, and GDNF in children with severe head injuries.
- To investigate the association between these neurotrophic factors and the severity and outcome of pediatric traumatic brain injury.
- To explore the potential role of neurotrophic factors in neuroprotection and recovery following TBI.
Main Methods:
- A prospective observational clinical study was conducted in a pediatric intensive care unit.
- Cerebrospinal fluid (CSF) and plasma samples were collected from 14 children with severe head injuries and 12 controls at 2 and 24 hours post-injury.
- Neurotrophic factor levels were quantified using an immuno-enzymatic assay.
Main Results:
- Patients exhibited significantly different mean levels of neurotrophic factors in CSF and plasma, with higher BDNF levels compared to NGF and GDNF.
- In CSF, NGF levels significantly increased, while BDNF levels significantly decreased from 2 to 24 hours post-injury; GDNF showed no significant change.
- While BDNF peaked early post-injury, only NGF expression in CSF was significantly associated with patient outcome (good vs. poor).
Conclusions:
- Altered neurotrophic factor levels suggest an endogenous neuroprotective response to biochemical changes after TBI.
- BDNF serves as an early indicator of brain injury in children.
- NGF levels in CSF are linked to favorable outcomes, suggesting a potential therapeutic role in managing severe pediatric head injuries.
Objectives:
We evaluated the neurotrophic factors [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glia-derived neurotrophic factor (GDNF)] expression and their association with the severity and outcome of children with traumatic brain injury.
Design:
Prospective observational clinical study.
Setting:
Pediatric intensive care unit.
Patients:
Fourteen children with severe head injury; 12 controls with obstructive hydrocephalus.
Measurement:
Cerebrospinal fluid (CSF) and plasma samples were collected 2 h (T1) and 24 h (T2) after head injury. Neurotrophic factor levels were measured using an immuno-enzymatic assay.
Main Results:
In patients, neurotrophic factor mean levels were significantly different in both CSF and plasma, showing high levels of BDNF compared to NGF and GDNF. Considering T1 and T2 expression, in the CSF the level of NGF increased from 3.5+/-0.4 pg/ml to 48.2+/-11.7 pg/ml ( p<0.001); BDNF decreased from 4854.0+/-1303.7 pg/ml to 593.0+/-114.8 pg/ml ( p<0.001), while GDNF did not undergo significant variations. In plasma, no significant changes were observed. Regarding severity and outcome, BDNF levels showed a sharp peak after head injury, but the only significant association was between NGF expression in the CSF and a good outcome versus a poor outcome ( p=0.007).
Conclusions:
The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after traumatic head injury. BDNF represents an early marker of brain injury, while NGF expression in the CSF was indicative of a good outcome and the role of this neurotrophin in the treatment of children with severe head injury may be hypothesized.