Plasma Brain-derived Neurotrophic Factor Levels Research Articles

A review of peripheral brain-derived neurotrophic factor levels in alcohol-dependent patients: Current understanding.

Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroplasticity of the brain, and its role in alcohol dependence has been explored in the recent past. Animal studies suggest that BDNF may function as a protective factor in transition from social drinking to an alcohol use disorder. However, clinical studies have not been able to establish similar findings and have shown mixed results. In order to obtain a comprehensive understanding, the current review aims to evaluate the existing literature on the role of BDNF in alcohol dependence. Articles were retrieved using search engines PubMed and Google Scholar. Original research studies focusing on human participants, published in English till October 2018 were reviewed. Studies which measured BDNF levels in serum or plasma or both were included in this study. A total of 13 studies were found which compared BDNF levels in alcohol-dependent patients with control population. The studies have mixed findings. Seven studies measured BDNF levels across the abstinence period, and most of the studies show improving BDNF levels across the abstinence. The current review supports the notion that BDNF plays an important role in the neuroplasticity of alcohol dependence. However, it is premature at this stage to draw conclusions that BDNF may be used as a biomarker, as there have been inconclusive findings when compared with control population. Future studies with longer follow-ups, larger sample size, comparing early and late periods of alcohol abstinence are required for better understanding of the role BDNF in alcohol dependence.

Impact of BDNF and sex on maintaining intact memory function in early midlife

Sex steroid hormones and neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), play a significant neuroprotective role in memory circuitry aging. Here, we present findings characterizing the neuroprotective effects of BDNF on memory performance, as a function of sex and reproductive status in women. Participants (N = 191; mean age = 50.03 ± 2.10) underwent clinical and cognitive testing, fMRI scanning, and hormonal assessments of menopausal staging. Memory performance was assessed with the 6-Trial Selective Reminding Test and the Face-Name Associative Memory Exam. Participants also performed a working memory (WM) N-back task during fMRI scanning. Results revealed significant interactions between menopausal status and BDNF levels. Only in postmenopausal women, lower plasma BDNF levels were associated with significantly worse memory performance and altered function in the WM circuitry. BDNF had no significant impact on memory performance or WM function in pre/perimenopausal women or men. These results suggest that in postmenopausal women, BDNF is associated with memory performance and memory circuitry function, thus providing evidence of potential sex-dependent factors of risk and resilience for early intervention.

Exercise Intensity and Recovery on Circulating Brain-derived Neurotrophic Factor.

Brain-derived neurotrophic factor (BDNF) is an exercise-induced neurotropin mediating neuroprotection and synaptic plasticity. Although exercise intensity is implicated as a potentially important mediator of BNDF release after exercise, the optimal exercise stimulus (interval vs continuous) and intensity (submaximal vs supramaximal) for augmenting circulating BDNF levels remains unknown. Irisin, an exercise-driven myokine, may also contribute to neuroprotection by upregulating BDNF. To examine the response and recovery of plasma BDNF and irisin after acute exercise of differing intensities. Eight males (23.1 ± 3.0 yr of age; V˙O2max 51.2 ± 4.4 mL·kg·min) completed four acute exercise sessions: 1) moderate-intensity continuous training (MICT, 65% V˙O2max); 2) vigorous-intensity continuous training (VICT, 85% V˙O2max); 3) sprint interval training (SIT, "all out"); and 4) no exercise (CTRL). Blood was collected preexercise as well as immediately, 30 min, and 90 min postexercise. Plasma BDNF and irisin were assessed with commercially available enzyme-linked immunosorbent assay kits. Plasma BDNF levels increased immediately after exercise in the SIT group (P < 0.0001) with plasma concentrations recovering 30 and 90 min postexercise. The BDNF levels after MICT were reduced 30 min postexercise compared with immediately postexercise (P = 0.0189), with no other changes across time points in MICT and VICT groups. Plasma BDNF area under the curve in SIT was significantly higher compared with CTRL, MICT, and VICT (P = 0.0020). No changes in plasma irisin across exercise groups and time points were found (P > 0.9999). Plasma BDNF levels increased in an intensity-dependent manner with SIT eliciting the highest BDNF concentration immediately postexercise. These results identify SIT as a time-efficient exercise modality to promote brain health through BDNF release.

PUFAs, BDNF and lipoxin A4 inhibit chemical-induced cytotoxicity of RIN5F cells in vitro and streptozotocin-induced type 2 diabetes mellitus in vivo

ObjectiveTo study whether minimal doses of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and lipoxin A4 (LXA4) and brain-derived neurotrophic factor (BDNF), when used in combination can protect RIN5F cells from chemical-induced cytotoxicity. As a corollary, to know whether plasma BDNF and LXA4 are altered in STZ-induced type 2 DM animals.Materials and methodsRIN5F cells, alloxan (AL), streptozotocin (STZ), doxorubicin (DB), and benzo(a)pyrene (BP) were used in this study. Chemical-induced apoptosis and changes in antioxidants, lipid peroxides and nitric oxide (NO) and LXA4 and BDNF levels in RIN5F cells were studied. Alterations in plasma concentrations of BDNF and LXA4 in STZ-induced type 2 diabetes animals was estimated.ResultsBDNF, LXA4 and AA, EPA and DHA protected (P < 0.001 and P < 0.01 respectively) against AL/STZ/DB/BP-induced toxicity to RIN5F cells in vitro. AL/ STZ/DB/BP inhibited BDNF and LXA4 production by RIN5F cells and were restored to normal by AA, EPA and DHA. Sub-optimal doses of BDNF, LXA4, AA and EPA when used in combination protected against cytotoxic action of AL/STZ/DB/BP on RIN5F cells in vitro by restoring LXA4/BDNF levels and altered antioxidant/lipid peroxides/NO levels (P < 0.01) to normal. STZ (65 mg/kg)-induced type 2 diabetes mellitus animals showed reduced plasma BDNF and LXA4 levels (P < 0.001).DiscussionAL/STZ/DB/BP-induced cytotoxicity to RIN5F cells in vitro can be prevented by BDNF, LXA4 and AA. AL/STZ/DB/BP are cytotoxic, possibly, by suppressing the production of LXA4 and BDNF in RIN5F cells. STZ-induced type 2 DM animals have decreased plasma levels of LXA4 and BDNF.ConclusionThe results of the present study suggest that BDNF, LXA4, EPA, DHA, AA, GLA and BDNF protect pancreatic β cells from the cytotoxic action of various chemicals and prevent development of diabetes mellitus. LXA4 seems to be the mediator of these cytoprotective actions of BDNF and PUFAs suggesting a close interaction exists among these molecules (BDNF, PUFAs and LXA4). Hence, methods developed to deliver a combination of PUFAs (especially AA), LXA4 and BDNF may prevent development of diabetes mellitus (both type 1 and type 2).

High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels

No studies have examined the relationship between endogenous polyunsaturated fatty acids (PUFAs) levels and treatment response to PUFAs. We conducted a 12-week, double-blind, placebo-controlled trial comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.2 g) and placebo on cognitive function (continuous performance test) in n = 92 youth (age 6–18-years-old) with Attention Deficit Hyperactivity Disorder (ADHD). Blood erythrocytes PUFAs were measured before and after treatment, to examine the effects of baseline endogenous EPA levels on treatment response and the effects of EPA treatment on PUFAs levels. Secondary measures included other ADHD symptoms, emotional symptoms, and levels of plasma high-sensitivity c-reactive protein (hs-CRP) and brain-derived neurotrophic factor (BDNF). Overall, EPA group improved more than placebo group on focused attention (variability, Effect size (ES) = 0.38, p = 0.041); moreover, within youth with the lowest baseline endogenous EPA levels, EPA group improved more than placebo group in another measure of focused attention (hit reaction time, HRT, ES = 0.89, p = 0.015) and in vigilance (HRT interstimulus interval changes, HRTISIC, ES = 0.83, p = 0.036). Interestingly, EPA group improved less than placebo group in impulsivity (commission errors), both overall and in youth with the highest baseline EPA levels, who also showed less improvement in other ADHD and emotional symptoms. EPA increased blood erythrocytes EPA by 1.6-fold but not DHA levels, and did not affect hs-CRP and BDNF plasma levels. In conclusion, EPA treatment improves cognitive symptoms in ADHD youth, especially if they have a low baseline endogenous EPA level, while youth with high EPA levels may be negatively affected by this treatment.

Brain-derived neurotrophic factor levels in pediatric sickle cell disease.

Children with sickle cell disease (SCD) have an increased risk of neurological complications, particularly stroke and silent cerebral infarction (SCI). Brain-derived neurotrophic factor (BDNF) is a nerve growth factor associated with neuronal survival, synaptic plasticity, elevated transcranial Doppler (TCD) velocities and increased risk of stroke in patients with SCD. The objective of this study was to analyze plasma BDNF protein levels in children with SCD participating in the Silent Cerebral Infarct Transfusion Multi-Center Clinical Trial (SIT Trial), comparing plasma samples of children with SCD and SCI to plasma samples from children with SCD without SCI, as well as healthy pediatric control participants. Entry, exit, and longitudinal blood samples were collected from 190 SIT Trial participants with SCD and healthy pediatric controls over time. BDNF levels were measured by enzyme-linked immunosorbent assay. Sample collection was not optimized for measurements of BDNF, but factors affecting BDNF levels were accounted for in analyses. BDNF levels were significantly higher in children with SCD in comparison to healthy pediatric control subjects. BDNF levels significantly increased over time in SCD participants. BDNF levels did not show any significant associations with the presence or absence of SCI or new/progressive SCI/stroke or TCD velocities. Plasma BDNF levels are elevated and increase over time in children with SCD. Additional studies with more longitudinal samples are needed to address the reasons for those increased levels.

Plasma BDNF Levels Are Associated with Stroke in Children with SCD

Background: Cerebrovascular disease, particularly overt stroke, is one of the most critical clinical complications of sickle cell disease (SCD). Individual stroke risk for patients with SCD is assessed by measuring trans-cranial Doppler ultrasound (TCD) velocity. While TCD screening and resulting use of chronic blood transfusion therapy in patients with abnormal TCDs has reduced stroke incidence in patients with SCD from 11% to 1%, the test has significant limitations. It can only be performed on children old enough to remain still for the assessment, or young enough to have open bony windows; typically 2-16 years of age. Additionally the test has poor positive predictive value, causing patients to be placed on chronic transfusion therapy who would not have gone on to have a stroke. Hydroxyurea (HU) is replacing chronic transfusion therapy in many institutions for primary stroke prevention, but many sites initiate a "cooling off" period of transfusions prior to initiating HU, and transfusion therapy may be indicated for abnormal TCD velocities in patients already on HU. The pathophysiology of stroke in SCD patients is not completely understood, but vascular remodeling, abnormal cerebral blood flow, and vaso-occlusion all play a role. Plasma levels of Brain derived neurotrophic factor (BDNF), myeloperoxidase (MPO), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) have been shown to be associated with high trans-cranial Doppler ultrasound (TCD) velocity in children with SCD; but there is limited data on their potential association with stroke in this population. BDNF is a neurotropin that is responsive to hypoxia and promotes neurogenesis as well as playing a key role in the regulation of the cell survival pathway; myeloperoxidase (MPO) promotes vascular injury by oxygen radical generation, leukocyte/neutrophil recruitment, and oxidative stress; vascular cell adhesion molecule 1 (VCAM-1) is and endothelial adhesion molecule involved in the pathophysiology of vaso-occlusion in SCD through promoting RBC adhesion; and intercellular adhesion molecule 1 (ICAM-1) is expressed on endothelial and immune system cells and is thought to be a ligand for leukocyte adhesion. We hypothesized that BDNF, MPO, VCAM-1 and ICAM-1 may be involved in stroke in SCD, and may be potential biomarkers to be used to assess an individual with SCD's stroke risk in addition to TCD. Methods: We collected plasma samples from the peripheral blood of fifteen SCD patients (HbSS) at the time of either silent cerebral infarct (SCI) or stroke. Stroke (n=8) or SI was confirmed by MRI using diffusion imaging and T2 FLAIR. The cohort included 6 females and 9 males between the ages of 3 and 20 years. Plasma from fifteen age and gender matched control patients with HbSS but had normal MRIs and TCD velocities less than 170 m/s. We measured plasma levels of BDNF, MPO, VCAM-1 and ICAM-1 using antibody immobilized fluorescent beads (Millipore, Billerica, MA) and Luminex xMAP technology (Bio-Rad, Hercules, CA). Student's t-test was used to analyze the difference in plasma levels between the stroke and control groups. Results and Conclusions: BDNF levels were significantly higher in the stroke group than in the control group; 2978.2 ± 960.3 pg/ml compared to 2200.8 ± 758.4 pg/ml, p=0.005. Difference in MPO levels between the two groups approached significance; 36617.2 ± 14828.9 pg/ml compared to 29521.9 ± 7889.6 pg/ml, p=0.07. Difference in VCAM-1 levels also approached significance; 143997.0 ± 9963.8 pg/ml compared to 138126.9 ± 11902.0 pg/ml, p=0.08, but there was no significant difference in ICAM-1 levels. Only BDNF plasma levels positively correlated with the area and volume of the infarct, p=0.009. These results further support the assertion that BDNF is involved in the pathophysiology of cerebrovascular disease in SCD. It is possible that MPO and VCAM-1 may also play a role, and that a significant difference was not found due to sample size limitations. Plasma BDNF levels, and possibly MPO and VCAM-1 plasma levels, have potential as biomarkers for stroke risk to improve the positive predictive value of TCD velocities in patients with SCD, or to assess risk in patients unable to receive TCDs. Disclosures No relevant conflicts of interest to declare.

Human Plasma BDNF Is Associated With Amygdala-Prefrontal Cortex Functional Connectivity and Problem Drinking Behaviors.

BackgroundPreclinical studies suggest that decreased levels of brain-derived neurotrophic factor in the amygdala play a role in anxiety and alcohol use disorder. The association between brain-derived neurotrophic factor levels and amygdala function in humans with alcohol use disorder is still unclear, although neuroimaging studies have also implicated the amygdala in alcohol use disorder and suggest that alcohol use disorder is associated with disrupted functional connectivity between the amygdala and prefrontal cortex during aversive states.MethodsThe current study investigated whether plasma brain-derived neurotrophic factor levels in individuals with and without alcohol use disorder (n = 57) were associated with individual differences in amygdala reactivity and amygdala-prefrontal cortex functional connectivity during 2 forms of aversive responding captured via functional magnetic resonance imaging: anxiety elicited by unpredictable threat of shock and fear elicited by predictable threat of shock. We also examined whether brain-derived neurotrophic factor and brain function were associated with binge drinking episodes and alcohol use disorder age of onset.ResultsDuring anxiety, but not fear, lower levels of plasma brain-derived neurotrophic factor were associated with less connectivity between the left amygdala and the medial prefrontal cortex and the inferior frontal gyrus. In addition, within individuals with alcohol use disorder (only), lower levels of brain-derived neurotrophic factor and amygdala-medial prefrontal cortex functional connectivity during anxiety were associated with more binge episodes within the past 60 days and a lower age of alcohol use disorder onset. There were no associations between brain-derived neurotrophic factor levels and focal amygdala task reactivity.ConclusionsTogether, the results indicate that plasma brain-derived neurotrophic factor levels are related to amygdala circuit functioning in humans, particularly during anxiety, and these individual differences may relate to drinking behaviors.

Ketamine-induced changes in plasma brain-derived neurotrophic factor (BDNF) levels are associated with the resting-state functional connectivity of the prefrontal cortex

Objectives Synaptic plasticity and brain-derived neurotrophic factor (BDNF) signalling are proposed to play key roles in antidepressant drug action. Ketamine, an N-methyl-D-aspartate receptor antagonist and putative antidepressant, may increase synaptic plasticity in prefrontal cortex through higher expression of BDNF. Furthermore, ketamine was shown to change resting-state functional connectivity (RSFC) of dorsomedial prefrontal cortex (dmPFC). Methods In a randomised, placebo-controlled study, we investigated acutely (100 min) and at 24 h following subanesthetic ketamine infusion which dmPFC seeded RSFC changes are most strongly associated with plasma BDNF level changes in 53 healthy participants (21 females, age: 24.4 ± 2.9 years) using 7 T-fMRI. Results We observed higher relative levels of BDNF 2 h and 24 h after ketamine compared to placebo. Whole-brain regression revealed that the change in BDNF after 24 h was associated with RSFC decreases from dmPFC to posterior cingulate cortex and ventromedial PFC at 24 h and exploratively also at the 100 min measurement point. Follow-up analyses revealed that RSFC reductions following ketamine were restricted to subjects showing increased BDNF levels at 24 h. Conclusions Our findings indicate BDNF level dynamics following ketamine are related to acute and 24 h RSFC changes. Particularly when BDNF increases are observed after ketamine infusion, a disconnection from dmPFC after 24 h is seen and may reflect synaptic plasticity effects.

Effect of continuous environmental enrichment and aerobic exercise on rat plasma and hippocampal brain-derived neurotrophic factor

Objective: Environmental enrichment (EE) or exercise can positively affect memory function through increased long-term potentiation and neurogenesis, which is facilitated by brain-derived neurotrophic factor (BDNF). BDNF promotes blood vessel growth, angiogenesis linked to adult neurogenesis, and neuronal survival. Here, we investigated the effects of EE, aerobic exercise, and their combination on plasma and hippocampal BDNF levels. Materials and Methods: Twenty-four 7-month-old adult male Wistar rats weighing 300–400 g were randomly assigned to the following four groups: control (C), aerobic exercise (A), EE, and combined EE and aerobic exercise (EEA). Interventions were given for 8 weeks, and plasma and hippocampal BDNF levels were measured using enzyme-linked immunosorbent assay. Results: A combination of aerobic exercise and continuous EE produced the largest increase in hippocampal and plasma BDNF levels in adult rats. A positive correlation (r = 0.686, P = 0.002, n = 24) was observed between plasma and hippocampal BDNF levels in adult rats. Conclusion: We conclude that a combination of aerobic exercise and continuous EE increases plasma and hippocampal BDNF in adult rats.

No evidence for altered plasma NGF and BDNF levels in fibromyalgia patients

There has been a surging interest in the putative role of peripheral growth factors in the pathophysiology of fibromyalgia, specifically in the peripheral sensitization that occurs in chronic pain disorders. This cross-sectional study set out to assess and compare brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in plasma samples from fibromyalgia patients and healthy controls. Plasma BDNF and NGF were measured in 89 fibromyalgia patients and 36 pain-free controls, and compared using ANCOVA controlling for potential confounders, as well as Bayesian methods for parameter estimation and model evaluation. BDNF and NGF levels in fibromyalgia patients did not differ from those in pain-free controls. Statistical methods were consistent, with both frequentist and Bayesian approaches leading to the same conclusions. Our study fails to replicate the finding that peripheral BDNF is altered in fibromyalgia, and instead our findings suggest that plasma levels of growth factor appear normative in fibromyalgia.

Peripheral Brain-Derived Neurotrophic Factor and Contactin-1 Levels in Patients with Attention-Deficit/Hyperactivity Disorder.

Brain-derived neurotrophic factor (BDNF) facilitates neuronal growth and plasticity, and is crucial for learning and memory. Contactin-1 (CNTN1) is a member of the subfamily of neural immunoglobulin and is involved in the formation of axon connections in the developing nervous system. This cross-sectional study investigates whether BDNF and CNTN1 affect susceptibility to attention deficit/hyperactivity disorder (ADHD). A total of 136 drug-naïve patients with ADHD (108 boys and 28 girls) and 71 healthy controls (45 boys and 26 girls) were recruited. Blood samples were obtained to measure the plasma levels of BDNF and CNTN1 in each child. We found that BDNF levels in the ADHD boys exceeded those in the control boys, but BDNF levels in the ADHD girls were lower than those in the control girls. Boys who had higher BDNF levels performed worse on the Wechsler Intelligence Scale for Children—Fourth Edition, but girls who had higher BDNF levels made fewer omission errors in the Conners’ Continuous Performance Test. However, CNTN1 level did not differ significantly between patients and controls, and were not correlated to ADHD characteristics, regardless of gender. The findings suggest BDNF may influence sex-specific susceptibility to ADHD, but CNTN1 was not associated with ADHD pathophysiology.

Correlation between interleukin-6 levels and methadone maintenance therapy outcomes

BackgroundThe outcome of methadone maintenance therapy (MMT) varies in each patient with opioid use disorder (OUD). Opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neurotrophic factor expression, and possibly leads to a vicious cycle that hinders recovery. Therefore, we investigated whether markers of inflammation and neurotrophic expression correlate with the MMT outcomes in OUD patients. MethodWe investigated OUD patients undergoing MMT and followed them up for 12 weeks. We measured plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-1β, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF), urinary morphine tests, and plasma morphine levels at baseline and on weeks 1, 4, 8, and 12 during MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the cytokine and BDNF levels and MMT outcomes. ResultsWe initially enrolled 104 patients, but only 78 patients completed end-of-study assessments. Plasma levels of CRP, TGF-β1, and BDNF fell during MMT. Plasma IL-6 levels were significantly associated with plasma morphine levels (P = 0.005) and urinary morphine-positive (+) results (P = 0.04), and significantly associated with poor compliance (P = 0.009) and early dropout from MMT (P = 0.001). However, other cytokine and BDNF levels were not consistently associated with MMT outcomes. ConclusionHigher IL-6 levels were associated with poor MMT outcomes. Additional studies on regulating IL-6 expression to improve treatment outcomes in OUD patients might be warranted.

Plasma brain-derived neurotrophic factor (BDNF) levels in inpatients with a stress-related adjustment or depressive disorder increase after multimodal inpatient treatment

Plasma brain-derived neurotrophic factor (BDNF) levels in inpatients with a stress-related adjustment or depressive disorder increase after multimodal inpatient treatment

Associations between serum and plasma brain-derived neurotrophic factor and influence of storage time and centrifugation strategy

The aims of the study were to clarify the impact of storage time and centrifugation strategy on brain-derived neurotrophic factor (BDNF) levels in human serum and plasma samples. In addition, we analyzed associations between BDNF levels, cardiorespiratory fitness and waist circumference. Seventeen healthy males (25.2 (4.1) years) were included in the study. Blood samples were drawn after an overnight fast and treated to different protocols, varying in time before centrifugation and centrifugation strategy. BDNF was analyzed in serum, normal plasma (NP) and platelet-poor plasma (PPP). Also, waist circumference and cardiorespiratory fitness were measured. A large increase was observed in serum BDNF levels during the first hour of clotting. BDNF in NP correlated with PPP, whereas no correlations were found between BDNF in serum and plasma. Though not statistical significant, correlations between fitness and BDNF in serum changed from positive at 30 min. to negative when clotting time was ≥60 min. In conclusion, BDNF levels in serum were affected by clotting time, whereas BDNF levels in plasma were influenced by centrifugation strategy. Importantly, BDNF in serum and plasma appears to reflect two different pools of BDNF. The biological relevance of the velocity of BDNF release during clotting and its dependence upon fitness must be investigated further.

Elevated plasma BDNF levels are correlated with NK cell activation in patients with traumatic spinal cord injury

BackgroundThe precise role of innate immune responses in the early stage of traumatic spinal cord injury (SCI), especially those mediated by natural killer (NK) cells, is poorly understood. MethodsThe frequency and phenotype of NK cells from traumatic SCI patients and healthy controls were assessed by flow cytometry. ELISA assay was used to detect the production of a series of cytokines, neurotrophins, and neurohormones in plasma samples. In vitro cell culture was performed to observe brain-derived neurotrophic factor (BDNF)-induced NK cell activation. ResultsA significant increase in the NK cell frequency and the presence of NK cells with the activated phenotype was observed, as reflected by the enhanced expression of CD69, HLA-DR, NKG2D, and NKp30 on the NK cells, in traumatic SCI patients within 24 h of injury, compared to case for the healthy controls. Meanwhile, a higher level of BDNF, a member of the neurotrophin family, was observed in the plasma samples of the SCI patients; the elevated level of BDNF was strongly and positively correlated with the percentage of NK cells during the early stage of traumatic SCI. Furthermore, the expression of CD69 and NKp30 on the NK cells increased following stimulation with BDNF for 24 h in vitro, which is consistent with the in vivo observation in SCI patients. ConclusionCollectively, our findings demonstrate the activation of NK cells within 24 h after traumatic SCI, and reveal a novel role of BDNF in regulating NK cell activation.

Whole Body Vibration Training on Muscle Strength and Brain-Derived Neurotrophic Factor Levels in Elderly Woman With Knee Osteoarthritis: A Randomized Clinical Trial Study.

Background: Osteoarthritis of the knee (kOA) is a chronic, progressive, degenerative health condition that contributes to the imbalance between the synthesis and destruction of articular cartilage. Recently, whole body vibration (WBV) training has been recommended as an effective alternative for strength training in elderly people, and various physiological effects are obtained in response to exercise performed on a vibratory platform, such as an increase in muscle activation and improved muscle performance. However, the effects of WBV particularly on the strength of the quadriceps muscle and neuronal plasticity are unknown.Objective: The aim of this study was to evaluate the effects of adding WBV to squat training on the isometric quadriceps muscle strength (IQMS) and the plasma levels of brain-derived neurotrophic factor (BDNF) in elderly woman with kOA.Methods: Fifteen elderly women ≥65 years of age with kOA were randomized into two interventions: (1) the vibration group (VG), in which participants performed squat exercise training in association with WBV or (2) the exercise group (EG), in which participants performed squat exercise training without vibration, for 12 weeks 3×/week.Results: Compared to the EG group, the VG group demonstrated a significantly greater delta (Δ) in IQMS values (IC95% 0.43–7.06; p ≤ 0.05) and in Δ BDNF plasma levels (IC95% −32.51 to 4.217; p ≤ 0.05) after the intervention period. There was an association between increase of Δ BDNF plasma levels and increase of Δ IQMS (β = 0.57; R2 = 0.32; p = 0.03).Conclusion: The addition of WBV to squat exercise training improves lower limb muscle performance in elderly women with kOA. These findings suggest that the improvement in muscle performance is related to neuromuscular adaptations induced by WBV.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03918291.

Plasma Brain‐Derived Neurotrophic Factor (BDNF) and serum cortisol levels in a sample of workers exposed to occupational stress and suffering from Adjustment Disorders

IntroductionDecreased plasma BDNF (pBDNF) levels have been proposed as a biomarker in illness phases of mood disorders. Serum cortisol (seC) levels are an index of energy mobilization and stress. The aim of this cross‐sectional study was to evaluate pBDNF and seC levels in workers exposed to occupational stress and suffering from Adjustment Disorders (AD) compared to healthy workers.MethodsPlasma BDNF and seC levels were measured by means of specific immunoassays in 64 AD patients and 38 healthy controls. Perceived and occupational stress was evaluated in patients and controls using the Psychological Stress Measure (PSM) and the Job Content Questionnaire (JCQ). Psychopatological symptoms in patients were assessed using specific rating scales.ResultsPlasma BDNF levels resulted significantly higher in patients than in controls, whereas no significant differences were found for seC levels. In patients but not in controls pBDNF levels showed a significant positive correlation with seC levels. Perceived stress levels were positively correlated with all psychopatological rating scales scores.ConclusionsBDNF could play a key role in the pathophysiology of stress‐related disorders and its peripheral levels elevation could contribute to protect neurons under stress. Further research is needed focusing on biomarkers for stress‐related disorders as a potential tool for the diagnosis and prevention of occupational diseases.

Blood heavy metals and brain-derived neurotrophic factor in the first trimester of pregnancy among migrant workers.

BackgroundLead, mercury, cadmium and arsenic are the priority heavy metals of major public health concern in industrialized countries. Exposure to them can cause cognitive impairment and depressive disorders through an effect on Brain-derived neurotrophic factor (BDNF) which is an important biomarker of pregnancy. Despite a number of prior studies on heavy metals pollution, there is few of studies on the effect of heavy metals on BDNF during early pregnancy. This study aims to examine the association between maternal blood heavy metals concentrations and BDNF during the first trimester pregnancy among Myanmar migrants in Thailand.MethodologyThis cross sectional study, a part of ongoing birth cohort was conducted at the antenatal care clinic from June to October 2018. A total of 108 with Myanmar migrant pregnancy with a single viable fetus of 0 to 14 gestation weeks who stayed within the industrial plant at least 3 months before were recruited. Socio-demographic characteristics and health behaviors were accessed using a self-report questionnaire. Maternal blood heavy metals (lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As)) were measured using an inductively coupled plasma mass spectrometer and plasma BDNF was measured using an enzyme-linked immunosorbent assay. Multivariate binary logistic regression were modeled to access the association.ResultsMedian (interquartile rank: IQR) concentrations were: BDNF (6.49 (1.79) μg/ml), Pb (2.77 (1.46) μg/dL), Hg (0.62 (0.54) μg/dL), Cd (0.93(0.86) μg/L) and As (0.40 (0.11) μg/dL) respectively. We categorized BDNF concentrations into high (> median) (n = 54) and low (≤ median) (n = 54) groups. After adjusting for potential confounders, high blood total arsenic concentration had 2.6-fold increased odds (aOR = 2.603, 95% CI: 1.178, 5.751) of low plasma BDNF level as compared with low blood total arsenic group. However, there was no significant association between BDNF and Pb, Hg and Cd.ConclusionsThe present findings demonstrate higher blood total arsenic level were more likely to have lower BDNF in early pregnancy. Our study suggested that heavy metal could be worsen BDNF level which plays its important role on biological effect of maternal depressive disorder and newborn neurodevelopment.

Plasma Biomarkers as Potential Predictors of Functional Dependence in Daily Life Activities after Ischemic Stroke: A Single Center Study.

Objective:Despite advances made in the treatment of ischemic stroke, it still remains one of the leading causes of mortality and disability worldwide. The main objective of this study was to identify from a panel of 10 inflammatory markers and chemokines those biomarkers that have a potential predictive role in the evolution of disability and functional dependence in daily activities after an ischemic stroke.Methods:The study included 116 patients with ischemic stroke and 40 healthy volunteers matched for gender and age. Stroke severity was assessed by the National Institute of Health Stroke Scale (NIHSS) on admission and during hospitalization and functional mobility in daily activities by Barthel index (BI). Multiplex panel with 10 biomarkers [brain-derived neurotrophic factor (BDNF), platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB, neural cell adhesion molecule (NCAM), cathepsin D, soluble vascular cell adhesion molecule (sVCAM), soluble intercellular cell adhesion molecule (sICAM), myeloperoxidase (MPO), regulated on activation, normal T cell expressed and secreted (RANTES), plasminogen activator inhibitor (PAI)-1] was analyzed on days 1 and 5 after admission using the xMAP technology.Results:Plasma concentrations of RANTES and NCAM were significantly lower in patients with ischemic stroke compared with healthy controls, while MPO and sICAM were significantly higher in patients versus controls. Plasma concentrations of sICAM, sVCAM, and RANTES significantly decreased during the analyzed period. For the first-day measurement, the bivariate analysis revealed the association of NIHSS on admission with sVCAM, and on discharge negative association with PDGF-AA, PDGR-AB/BB, BDNF, and RANTES. Plasma levels of PDGF-AA, PDGF-AB/BB, BDNF, and RANTES were found to be significantly lower in patients with BI ≤ 80, on day 5 after disease onset. PDGF-AA, PDGF-AB/BB, and BDNF were univariate and multivariate predictors for functional dependence in daily life activity (BI ≤ 80), having a protective effect (odds ratio < 1).Conclusion:Plasma levels of BDNF, PDGF-AA, and PDGF-AB/BB are independent predictors for functional dependency in daily life activities and may be useful prognostic markers in the evaluation of ischemic stroke patients.