Article

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.

Langue : ANGLAIS