Variation in the BDNF gene interacts with age to predict mortality in a prospective, longitudinal cohort with severe TBI
Michelle D. Failla,Raj G. Kumar,Andrew B. Peitzman,Yvette P. Conley,Robert E. Ferrell,Amy K. Wagner +5 more
TLDR
Data suggest complex relationships between BDNF and TBI mortality that interact with age to influence survival predictions beyond clinical variables alone, and evidence supporting dynamic, temporal balances of pro-survival/pro-apoptotic target receptors may explain injury and age-related gene associations.Abstract:
Background. Mortality predictions following traumatic brain injury (TBI), and our understanding of TBI pathology, may be improved by including genetic risk in addition to traditional prognostic variables. One promising target is the gene coding for brain-derived neurotrophic factor (BDNF), a ubiquitous neurotrophin important for neuronal survival and neurogenesis. Objective. We hypothesized the addition of BDNF genetic variation would improve mortality prediction models and that BDNF Met-carriers (rs6265) and C-carriers (rs7124442) would have the highest mortality rates post-TBI. Methods. This study examined BDNF functional single nucleotide polymorphisms rs6265 (val66met) and rs7124442 (T>C) in relation to mortality in a prospective, longitudinal cohort with severe TBI. We examined 315 individuals receiving care for a closed head injury within the University of Pittsburgh Medical Center, aged 16 to 74 years. Mortality was examined acutely (0-7 days postinjury) and postacutely (8-365 days postinjury). A g...read more
Citations
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Journal ArticleDOI
Pathophysiology of Traumatic Brain Injury.
TL;DR: The pathogenesis of focal versus diffuse brain damage is presented for consideration of its overall implications for morbidity and the influence of premorbid factors including age, genetics, and socioeconomic background is discussed.
Journal ArticleDOI
Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome.
Raj G. Kumar,Matthew L. Diamond,Jennifer A. Boles,Rachel P. Berger,S.A. Tisherman,Patrick M. Kochanek,Amy K. Wagner +6 more
TL;DR: Evidence is provided that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases areassociated with increased odds for unfavorable global outcomes in the first year following TBI.
Journal ArticleDOI
Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders
TL;DR: Because many BDNF polymorphisms and non-genetic factors have been implicated in the complex traits of neuropsychiatric diseases, the conventional genetic association-based method is limited to address these complex interactions.
Journal ArticleDOI
The Role of BDNF in Peripheral Nerve Regeneration: Activity-Dependent Treatments and Val66Met.
TL;DR: Preliminary data are presented on the effectiveness of one such activity-dependent treatment, electrical stimulation, in enhancing axon regeneration in mice expressing the met allele of the Val66Met polymorphism.
Journal ArticleDOI
Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related Mortality: Interrelationships Between Genetics and Acute Systemic and Central Nervous System BDNF Profiles.
TL;DR: BDNF levels predicted mortality, in addition to gene * age interactions, suggesting levels capture additional mortality risk, in the context of age and genetic risk.
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