PMID- 28337122
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 10
DP  - 2017
TI  - Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor 
      Relationships to Mortality after Severe TBI: A Prospective Cohort Study.
PG  - 44
LID - 10.3389/fnmol.2017.00044 [doi]
LID - 44
AB  - Distinct regulatory signaling mechanisms exist between cortisol and brain derived 
      neurotrophic factor (BDNF) that may influence secondary injury cascades 
      associated with traumatic brain injury (TBI) and predict outcome. We investigated 
      concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0-6 
      after severe TBI while accounting for BDNF genetics and age. We also determined 
      associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, 
      rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to 
      previously published hypothesized risk for mortality in "younger patients" (<48 
      years) and hypothesized BDNF production/secretion capacity with these variants. 
      Group based trajectory analysis (TRAJ) was used to create two cortisol groups 
      (high and low trajectories). A Bayesian estimation approach informed the 
      mediation models. Results show CSF BDNF predicted patient cortisol TRAJ group (P 
      = 0.001). Also, GRS moderated BDNF associations with cortisol TRAJ group. 
      Additionally, cortisol TRAJ predicted 6-month mortality (P = 0.001). In a 
      mediation analysis, BDNF predicted mortality, with cortisol acting as the 
      mediator (P = 0.011), yielding a mediation percentage of 29.92%. Mediation 
      effects increased to 45.45% among younger patients. A BDNF(*)GRS interaction 
      predicted mortality in younger patients (P = 0.004). Thus, we conclude 6-month 
      mortality after severe TBI can be predicted through a mediation model with CSF 
      cortisol and BDNF, suggesting a regulatory role for cortisol with BDNF's 
      contribution to TBI pathophysiology and mortality, particularly among younger 
      individuals with severe TBI. Based on the literature, cortisol modulated BDNF 
      effects on mortality after TBI may be related to known hormone and neurotrophin 
      relationships to neurological injury severity and autonomic nervous system 
      imbalance.
FAU - Munoz, Miranda J
AU  - Munoz MJ
AD  - Department of Physical Medicine and Rehabilitation, University of 
      PittsburghPittsburgh, PA, USA; Department of Biological Sciences, Carnegie Mellon 
      UniversityPittsburgh, PA, USA.
FAU - Kumar, Raj G
AU  - Kumar RG
AD  - Department of Physical Medicine and Rehabilitation, University of 
      PittsburghPittsburgh, PA, USA; Department of Epidemiology, University of 
      PittsburghPittsburgh, PA, USA.
FAU - Oh, Byung-Mo
AU  - Oh BM
AD  - Department of Physical Medicine and Rehabilitation, University of 
      PittsburghPittsburgh, PA, USA; Department of Rehabilitation Medicine, Seoul 
      National University HospitalSeoul, South Korea.
FAU - Conley, Yvette P
AU  - Conley YP
AD  - Department of Physical Medicine and Rehabilitation, University of 
      PittsburghPittsburgh, PA, USA; Department of Epidemiology, University of 
      PittsburghPittsburgh, PA, USA.
FAU - Wang, Zhensheng
AU  - Wang Z
AD  - Department of Nursing, University of PittsburghPittsburgh, PA, USA; Safar Center 
      for Resuscitation Research, University of PittsburghPittsburgh, PA, USA.
FAU - Failla, Michelle D
AU  - Failla MD
AD  - Department of Psychiatry, Vanderbilt University Medical Center Nashville, TN, 
      USA.
FAU - Wagner, Amy K
AU  - Wagner AK
AD  - Department of Physical Medicine and Rehabilitation, University of 
      PittsburghPittsburgh, PA, USA; Safar Center for Resuscitation Research, 
      University of PittsburghPittsburgh, PA, USA; Department of Neuroscience, 
      University of PittsburghPittsburgh, PA, USA; Center for Neuroscience, University 
      of PittsburghPittsburgh, PA, USA.
LA  - eng
PT  - Journal Article
DEP - 20170309
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5343043
OTO - NOTNLM
OT  - BDNF
OT  - TBI
OT  - biomarkers
OT  - cerebrospinal fluid
OT  - cortisol
OT  - genetics
EDAT- 2017/03/25 06:00
MHDA- 2017/03/25 06:01
PMCR- 2017/01/01
CRDT- 2017/03/25 06:00
PHST- 2016/10/23 00:00 [received]
PHST- 2017/02/09 00:00 [accepted]
PHST- 2017/03/25 06:00 [entrez]
PHST- 2017/03/25 06:00 [pubmed]
PHST- 2017/03/25 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2017.00044 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2017 Mar 9;10:44. doi: 10.3389/fnmol.2017.00044. eCollection 
      2017.