Serum Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Levels Are Associated With Risk of Stroke and Vascular Brain Injury Framingham Study
ABSTRACT Brain-derived neurotrophic factor (BDNF), a major neurotrophin and vascular endothelial growth factor (VEGF) have a documented role in neurogenesis, angiogenesis, and neuronal survival. In animal experiments, they impact infarct size and functional motor recovery after an ischemic brain lesion. We sought to examine the association of serum BDNF and VEGF with the risk of clinical stroke or subclinical vascular brain injury in a community-based sample.
In 3440 Framingham Study participants (mean age, 65±11 years; 56% women) who were free of stroke/transient ischemic attack (TIA), we related baseline BDNF and logVEGF to risk of incident stroke/TIA. In a subsample with brain MRI and with neuropsychological tests available (n=1863 and 2104, respectively; mean age, 61±9 years, 55% women, in each), we related baseline BDNF and logVEGF to log-white matter hyperintensity volume on brain MRI, and to visuospatial memory and executive function tests.
During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA. In multivariable analyses adjusted for age, sex, and traditional stroke risk factors, lower BDNF and higher logVEGF levels were associated with an increased risk of incident stroke/TIA (hazard ratio comparing BDNF Q1 versus Q2-Q4, 1.47; 95% confidence interval, 1.09-2.00; P=0.012 and hazard ratio/SD increase in logVEGF, 1.21; 95% confidence interval, 1.04-1.40; P=0.012). Persons with higher BDNF levels had less log-white matter hyperintensity volume (β±SE=-0.05±0.02; P=0.025), and better visual memory (β±SE=0.18±0.07; P=0.005).
Lower serum BDNF and higher VEGF concentrations were associated with increased risk of incident stroke/TIA. Higher levels of BDNF were also associated with less white matter hyperintensity and better visual memory. Our findings suggest that circulating BDNF and VEGF levels modify risk of clinical and subclinical vascular brain injury.
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ABSTRACT: The aim of the present study was to investigate the potential clinical application of the genetic marker microRNA (miRNA)-210 in the cerebrospinal fluid (CSF) and serum of patients with Alzheimer's disease (AD). The enrolled patients were divided into the mild cognitive impairment (MCI) and AD groups. Healthy individuals were used as the controls. The mRNA and protein expression of vascular endothelial growth factor (VEGF) in the CSF and serum samples was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The expression of miRNA-210 in the CSF and serum was detected by RT-qPCR. The results revealed that the mRNA and protein expression levels of VEGF in the CSF and serum were decreased in the MCI and AD groups compared with those in the control group. The greater the severity of the dementia, the lower the mRNA and protein expression of VEGF. Similar to the trend observed for VEGF, the miRNA-210 expression in the CSF and serum decreased as the severity of the AD increased. miRNA-210 is thus not only indicative of AD pathogenesis, but may also provide novel insights into the prevention and treatment of the disease.Experimental and therapeutic medicine 03/2015; 9(3):1013-1017. DOI:10.3892/etm.2015.2179 · 0.94 Impact Factor
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ABSTRACT: Hypoxic-ischemic brain damage (HIBD), a leading cause of perinatal disability and death, has limited therapeutic options. Stem cell therapy has been demonstrated as a potential novel therapy for neurological disorders. Compared with other types of stem cells, umbilical cord blood mesenchymal stem cells (UCB-MSCs) have several unique characteristics, such as a higher rate of cell proliferation and clonality. However, the limited life span of UCB-MSCs hinders their clinical application. Therefore, efforts are urgently needed to circumvent this disadvantage. Telomerase reverse transcriptase (TERT), which promotes cell proliferation and survival, plays a protective role in hypoxic-ischemic (HI) brain injury. Thus, it is reasonable to propose that UCB-MSCs modified by exogenous TERT expression might have a longer lifespan and increased viability. Moreover, brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates development, regeneration, survival and maintenance of neurons, facilitates post-injury recovery when administered by infusion or virus-mediated delivery. Therefore, TERT- and BDNF-modified UCB-MSCs may have a longer lifespan and also maintain neural differentiation, thus promoting the recovery of neurological function following hypoxic-ischemic brain damage (HIBD) and thereby representing a new effective strategy for HIBD in neonates.International Journal of Developmental Neuroscience 07/2014; DOI:10.1016/j.ijdevneu.2014.06.014 · 2.92 Impact Factor
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ABSTRACT: Background Depression is a frequent mood disorder that affects around a third of stroke patients and has been associated with poorer outcome. Our aim was to determine whether there is a relationship between serum Brain-derived neurotrophic factor (BDNF) levels and post-stroke depression (PSD). Methods Two hundred and sixteen ischemic stroke patients admitted to the hospital within the first 24 h after stroke onset were consecutively recruited and followed up for 3 months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for post-stroke depression at day 90. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of BDNF at admission. Multivariate analyses were performed using logistic regression models. Results In our study, 59 patients (27.3%) were diagnosed as having major depression at 3 months. Patients with major depression showed lower levels of serum BDNF [8.1 (5.6–9.4) vs. 13.7 (10.4–16.5)ng/ml, P<0.0001] at admission. In multivariate analyses, serum BDNF was an independent predictor of PSD at 3 months [odds ratio (OR): 0.79(0.72–0.87), P=0.003]. Serum levels of BDNF≤10.2 ng/ml were independently associated with post-stroke (OR, 11.5; 95% CI, 5.6–23.4, P<0.0001), after adjustment for possible variables. Conclusion The present study demonstrates a strong relationship between serum BDNF levels at admission and the development of PSD within 3 months. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options.Journal of Affective Disorders 10/2014; 168:373–379. DOI:10.1016/j.jad.2014.07.011 · 3.71 Impact Factor