====== Brain-derived neurotrophic factor ====== Brain-derived [[neurotrophic factor]] (BDNF) plays an important role in promoting the growth, differentiation, survival, and synaptic stability of neurons. It is important also for [[neuron]]al survival and [[regeneration]]. ---- Presently, the transplantation of [[neural stem cell]]s (NSCs) is known to induce neural repair to some extent after injury or disease. In as study, to investigate whether NSCs genetically modified to encode the BDNF gene (BDNF/NSCs) would further enhance synaptogenesis, BDNF/NSCs or naive NSCs were directly engrafted into lesions in a rat model of traumatic brain injury (TBI). Immunohistochemistry, western blotting and RT-PCR were performed to detect synaptic proteins, BDNF-TrkB and its downstream signaling pathways, at 1, 2, 3 or 4 weeks after transplantation. Our results showed that BDNF significantly increased the expression levels of the TrkB receptor gene and the phosphorylation of the TrkB protein in the lesions. The expression levels of Ras, phosphorylated Erk1/2 and postsynaptic density protein-95 were elevated in the BDNF/NSCs-transplanted groups compared with those in the NSCs-transplanted groups throughout the experimental period. Moreover, the nuclear factor (erythroid-derived 2)-like 2/Thioredoxin (Nrf2/Trx) axis, which is a specific therapeutic target for the treatment of injury or cell death, was upregulated by BDNF overexpression. Therefore, we determined that the increased synaptic proteins level implicated in synaptogenesis might be associated with the activation of the MAPK/Erk1/2 signaling pathway and the upregulation of the antioxidant agent Trx modified by BDNF-TrkB following the BDNF/NSCs transplantation after TBI ((Chen T, Wu Y, Wang Y, Zhu J, Chu H, Kong L, Yin L, Ma H. Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of Neural Stem Cells in a Rat Model of Traumatic Brain Injury. Neurochem Res. 2017 Aug 5. doi: 10.1007/s11064-017-2340-7. [Epub ahead of print] PubMed PMID: 28780733. )). ---- Korley et al. examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency departments (ED) of the Johns Hopkins Hospital (JHH, n=76) and San Francisco General Hospital (SFGH, n=80), and a control group of JHH ED patients without TBI (n=150). Findings were subsequently validated in the prospective, multi-center, Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study, n=159. We investigated the association between BDNF, Glial fibrillary acidic protein (GFAP) and Ubiquitin C-terminal hydrolase -L1 (UCH-L1) and recovery from TBI at 6 months in the TRACK-TBI Pilot cohort. Incomplete recovery was defined as having either post-concussive syndrome (PCS) or a Glasgow Outcome Scale Extended (GOSE) score<8 at 6 months. Median day-of-injury BDNF concentrations (ng/ml) were lower among TBI cases (JHH TBI: 17.5 and SFGH TBI: 13.8) than in JHH controls (60.3), p=0.0001. Among TRACK-TBI Pilot subjects, median BDNF concentrations (ng/ml) were higher in mild (8.3) than in moderate (4.3) or severe TBI (4.0), p=0.004. In the TRACK-TBI cohort, the 75 (71.4%) subjects with very low BDNF values (i.e.