title: Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related Mortality: Interrelationships Between Genetics and Acute Systemic and Central Nervous System BDNF Profiles.
abstract: BACKGROUND
  Older adults have higher mortality rates after severe traumatic brain injury (TBI) compared to younger adults. Brain-derived neurotrophic factor (BDNF) signaling is altered in aging and is important to TBI given its role in neuronal survival/plasticity and autonomic function. Following experimental TBI, acute BDNF administration has not been efficacious. Clinically, genetic variation in BDNF (reduced signaling alleles: rs6265, Met-carriers; rs7124442, C-carriers) can be protective against acute mortality. Postacutely, these genotypes carry lower mortality risk in older adults and greater mortality risk among younger adults.
  
  
  OBJECTIVE
  Investigate BDNF levels in mortality/outcome following severe TBI in the context of age and genetic risk.
  
  
  METHODS
  Cerebrospinal fluid (CSF) and serum BDNF were assessed prospectively during the first week following severe TBI (n = 203) and in controls (n = 10). Age, BDNF genotype, and BDNF levels were assessed as mortality/outcome predictors.
  
  
  RESULTS
  CSF BDNF levels tended to be higher post-TBI (P = .061) versus controls and were associated with time until death (P = .042). In contrast, serum BDNF levels were reduced post-TBI versus controls (P < .0001). Both gene * BDNF serum and gene * age interactions were mortality predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to be negatively correlated post-TBI (P = .07).
  
  
  CONCLUSIONS
  BDNF levels predicted mortality, in addition to gene * age interactions, suggesting levels capture additional mortality risk. Higher CSF BDNF post-TBI may be detrimental due to injury and age-related increases in pro-apoptotic BDNF target receptors. Negative CSF and serum BDNF correlations post-TBI suggest blood-brain barrier transit alterations. Understanding BDNF signaling in neuronal survival, plasticity, and autonomic function may inform treatment.
authors.affiliation: Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Failla
authors.affiliation: Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Health Promotion & Development, School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.affiliation: Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA wagnerak@upmc.edu.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wagner
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000235:genetics*; D005260:Female; D023261:Glasgow Outcome Scale; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF; Rehabilomics; aging; genetics; mortality; traumatic brain injury