脑源性神经营养因子（BDNF）与创伤性脑损伤相关死亡率：遗传学与急性全身及中枢神经系统BDNF概况之间的相互关系
Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related Mortality: Interrelationships Between Genetics and Acute Systemic and Central Nervous System BDNF Profiles.
作者信息
Failla Michelle D, Conley Yvette P, Wagner Amy K
机构信息
Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
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.
出版信息
Neurorehabil Neural Repair. 2016 Jan;30(1):83-93. doi: 10.1177/1545968315586465. Epub 2015 May 15.
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.
背景
与年轻成年人相比，老年成年人在重度创伤性脑损伤（TBI）后死亡率更高。脑源性神经营养因子（BDNF）信号在衰老过程中发生改变，鉴于其在神经元存活/可塑性和自主神经功能中的作用，对TBI很重要。实验性TBI后，急性给予BDNF无效。临床上，BDNF的基因变异（信号降低等位基因：rs6265，携带Met者；rs7124442，携带C者）可预防急性死亡。急性后期，这些基因型在老年成年人中死亡风险较低，而在年轻成年人中死亡风险较高。
目的
在年龄和遗传风险背景下，研究重度TBI后死亡率/预后中的BDNF水平。
方法
在重度TBI后的第一周（n = 203）及对照组（n = 10）中，前瞻性评估脑脊液（CSF）和血清BDNF。将年龄、BDNF基因型和BDNF水平评估为死亡率/预后预测指标。
结果
与对照组相比，TBI后脑脊液BDNF水平倾向于更高（P = 0.061），且与直至死亡的时间相关（P = 0.042）。相反，与对照组相比，TBI后血清BDNF水平降低（P < 0.0001）。在同一多变量模型中，基因BDNF血清和基因年龄相互作用均为TBI后死亡率预测指标。TBI后脑脊液和血清BDNF倾向于呈负相关（P = 0.07）。
结论
除基因*年龄相互作用外，BDNF水平可预测死亡率，提示其水平反映了额外的死亡风险。TBI后脑脊液BDNF水平较高可能因损伤和促凋亡BDNF靶受体的年龄相关增加而有害。TBI后脑脊液和血清BDNF的负相关提示血脑屏障转运改变。了解BDNF在神经元存活、可塑性和自主神经功能中的信号传导可能为治疗提供依据。
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