Brain-derived neurotrophic factor (BDNF) in traumatic brain injury-related mortality: Interrelationships between genetics and acute systemic and central nervous system BDNF profiles

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Study evaluated brain-derived neurotrophic factor (BDNF) levels, interactions with BDNF genetic variation, and mortality associations across the first year following traumatic brain injury (TBI). Cerebrospinal fluid (CSF) and serum BDNF were assessed prospectively during the first week following severe TBI in 203 subjects and in 10 control subjects. Age, BDNF genotype, and BDNF levels were assessed as mortality/outcome predictors. CSF BDNF levels tended to be higher post-TBI versus controls and were associated with time until death. In contrast, serum BDNF levels were reduced post-TBI versus controls. Both gene-by-BDNF serum and gene-by-age interactions were mortality predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to be negatively correlated post-TBI. Both CSF and serum BDNF demonstrated significant predictive capacity when assessing mortality over a 1-year recovery period, in addition to genetic risk, suggesting BDNF levels as a novel and informative TBI biomarker. The findings support further work exploring BDNF pathophysiology as a contributing factor to mortality following TBI. Understanding BDNF signaling in neuronal survival, plasticity, and autonomic function may inform treatment.

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