PMID- 25979196
OWN - NLM
STAT- MEDLINE
DCOM- 20161006
LR  - 20220408
IS  - 1552-6844 (Electronic)
IS  - 1545-9683 (Print)
IS  - 1545-9683 (Linking)
VI  - 30
IP  - 1
DP  - 2016 Jan
TI  - Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related 
      Mortality: Interrelationships Between Genetics and Acute Systemic and Central 
      Nervous System BDNF Profiles.
PG  - 83-93
LID - 10.1177/1545968315586465 [doi]
AB  - 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.
CI  - (c) The Author(s) 2015.
FAU - Failla, Michelle D
AU  - Failla MD
AD  - Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
FAU - Conley, Yvette P
AU  - Conley YP
AD  - 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.
FAU - Wagner, Amy K
AU  - Wagner AK
AD  - 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.
LA  - eng
GR  - R01 NR013342/NR/NINR NIH HHS/United States
GR  - R01 HD048162/HD/NICHD NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - R01NR008424/NR/NINR NIH HHS/United States
GR  - R01NR013342/NR/NINR NIH HHS/United States
GR  - R01HD048162/HD/NICHD NIH HHS/United States
GR  - R01 NR008424/NR/NINR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150515
PL  - United States
TA  - Neurorehabil Neural Repair
JT  - Neurorehabilitation and neural repair
JID - 100892086
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Adult
MH  - Biomarkers/blood/cerebrospinal fluid
MH  - Brain Injuries/*genetics/*metabolism/*mortality
MH  - Brain-Derived Neurotrophic Factor/*blood/*cerebrospinal fluid/*genetics
MH  - Female
MH  - Glasgow Outcome Scale
MH  - Humans
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
PMC - PMC4644728
MID - NIHMS683688
OTO - NOTNLM
OT  - BDNF
OT  - Rehabilomics
OT  - aging
OT  - genetics
OT  - mortality
OT  - traumatic brain injury
COIS- Conflict of Interest Statement: The authors declare no conflicts of interest.
EDAT- 2015/05/17 06:00
MHDA- 2016/10/08 06:00
PMCR- 2017/01/01
CRDT- 2015/05/17 06:00
PHST- 2015/05/17 06:00 [entrez]
PHST- 2015/05/17 06:00 [pubmed]
PHST- 2016/10/08 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 1545968315586465 [pii]
AID - 10.1177/1545968315586465 [doi]
PST - ppublish
SO  - Neurorehabil Neural Repair. 2016 Jan;30(1):83-93. doi: 10.1177/1545968315586465. 
      Epub 2015 May 15.