Acute effects of a session of electroconvulsive therapy on brain-derived neurotrophic factor plasma levels.

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are neurotrophins that play critical roles in brain neuronal function. Previous studies have established the association between BDNF and NGF signaling and severe mental disorders, but changes in BDNF plasma levels and electroconvulsive therapy (ECT) response are controversial. The aim of his study was to explore the acute effects of a single session of ECT on these neurotrophins signaling. Plasma levels of BDNF and NGF and their tyrosine kinase-type receptors expression in peripheral blood mononuclear cells (PBMCs) were determined before and two hours after a single ECT session in 30 subjects with a severe mental disorder. Two hours after an ECT session we found a statistically significant decrease of BDNF plasma levels (p=0.007). We did not find significant acute effects on NGF plasma levels or receptors expression in PBMCs. We found a significant inverse correlation between the time of convulsion and BDNF plasma levels decrease (r=-0.041, p=0.024). We have identified a decrease in BDNF plasma levels after 2h of a single ECT session. These results indicate the interest for future research in the role of neurotrophins in the response and safety of ECT.

The role of BDNF and NGF plasma levels in first-episode schizophrenia: A longitudinal study.

Neurotrophins have been proposed to be involved in biological mechanisms which might underlie different clinical outcomes in schizophrenia. The aims of the present study were to examine the BDNF/NGF plasma levels in a cohort of first-episode schizophrenia (FES) patients in remission as potential biological predictors of relapse; to study the associations between these neurotrophins and the symptomatology severity through different stages after a FES in two independent cohorts. 2EPs-Cohort: 69 first-episode in clinical remission were included. BDNF/NGF plasma levels and symptom severity were measured at enrollment and at 3-year or at the time of the second episode/relapse. FLAMM-PEPs-Cohort: 65 first-episodes were also included. BDNF/NGF and symptom severity were obtained at enrollment and 2-year follow-up. Symptomatology was assessed with the Marder-PANSS-Factor scores. Plasma neurotrophins did not differ significantly over time and neither BDNF/NGF were predictors of relapse. Besides, in remission stages, baseline BDNF levels showed significant correlations with both positive and negative symptoms (p<0.05); NGF, with negative symptomatology (p<0.01). Similarly, in the FLAMM-PEPs-Cohort, baseline BDNF/NGF levels showed significant correlations with negative symptoms (and not positive symptomatology) at follow-up (p<0.05). In both cohorts, lower levels correlated with higher symptom severity. Findings did not support a role for BDNF/NGF plasma levels as biomarkers of relapse in FES patients. Nevertheless, baseline BDNF/NGF may lead to be considered potentially useful biomarkers of long-term severity in schizophrenia and of the underlying illness traits, specially of negative symptomatology severity. More longitudinal studies in FES samples and adding a control group are warranted to replicate these findings.

Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders.

BACKGROUND: Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress. HYPOTHESIS/OBJECTIVE: The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). METHODS: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as Free Oxygen Radicals Test (FORT) and Free Oxygen Radicals Defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-ß, and TNF-α) involved in neuroinflammatory and oxidative processes have been investigated. RESULTS: We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children. CONCLUSION: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

Gender differences in ultradian serum levels of NGF and BDNF correlate with psychophysical traits in healthy humans.

We aimed at investigating the gender and/or ultradian pattern of serum levels of the Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Blood samples were collected at the 8.00, 13.00 and 20.00 hours of the day in healthy men and women, and the neurotrophins concentration was measured in the serum by ELISA. A further aim of the study was to evaluate whether or not the NGF/BDNF variations might be related to specific physiological or psychological traits as mood, feeling good and feeling rested, sexual desire and energy. Heart rate and blood pressure were also monitored at the same hours in each enrolled subject. The anxiety (STAI-T and STAI-S score) and sleeping quality were once evaluated in the morning too. We found that serum BDNF increases in men and decreases in women from morning to evening, while NGF shows a similar ultradian profile between men and women, but with higher concentrations in women. Both neurotrophins also show gender-related associations with psychophysiological variables. High NGF levels correlated with a high score for all the psychological variables in men, but with a low score in women. An inverse correlation was found between BDNF and energy and sexual desire in women, while no correlations were found in men. These data disclose that the condition of well-being (or activity/arousal status) is featured by an increasing NGF profile in men and a negative BDNF/NGF trend in women. The clinical relevance of the present data is discussed.

Plasma levels of nerve growth factor in Egyptian autistic children: Relation to hyperserotonemia and autoimmunity.

Hyperserotonemia and brain-specific autoantibodies are detected in some autistic children. Nerve growth factor (NGF) stimulates the proliferation of B lymphocytes with production of antibodies and also increases mast cell serotonin release. This work was the first to investigate the relationship between plasma NGF and both hyperserotonemia and the frequency of serum anti-myelin basic protein (anti-MBP) auto-antibodies in 22 autistic children aged between 4 and 12 years and 22 healthy-matched controls. Levels of NGF, serotonin and anti-MBP were significantly higher in autistic children than healthy control children (P < 0.001). There was a significant positive correlation between NGF and serotonin levels in autistic patients (P < 0.01). In contrast, there was a non-significant correlation between NGF and anti-MBP levels (P > 0.05). In conclusions, serum NGF levels were elevated and significantly correlated to hyperserotonemia found in many autistic children.

Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial.

BACKGROUND: Immunotherapy is being tested in early-stage non-small cell lung cancer (NSCLC), and achieving higher rates of complete pathological responses (CPR) as compared to standard of care. Early identification of CPR patients has vital clinical implications. In this study, we focused on basal peripheral immune cells and their treatment-related changes to find biomarkers associated to CPR. METHODS: Blood from 29 stage IIIA NSCLC patients participating in the NADIM trial (NCT03081689) was collected at diagnosis and post neoadjuvant treatment. More than 400 parameters of peripheral blood mononuclear cells (PBMCs) phenotype and plasma soluble factors were analyzed. RESULTS: Neoadjuvant chemoimmunotherapy altered more than 150 immune parameters. At diagnosis, 11 biomarkers associated to CPR were described, with an area under the ROC curve >0.70 and p-value <.05. CPR patients had significantly higher levels of CD4+ PD-1+ cells, NKG2D, and CD56 expression on T CD56 cells, intensity of CD25 expression on CD4+ CD25hi+ cells and CD69 expression on intermediate monocytes; but lower levels of CD3+ CD56- CTLA-4+ cells, CD14++ CD16+ CTLA-4+ cells, CTLA-4 expression on T CD56 cells and lower levels of b-NGF, NT-3, and VEGF-D in plasma compared to non-CPR. Post treatment, CPR patients had significantly higher levels of CD19 expression on B cells, BCMA, 4-1BB, MCSF, and PARC and lower levels of MPIF-1 and Flt-3L in plasma compared to non-CPR. CONCLUSIONS: Patients achieving CPR seem to have a distinctive peripheral blood immune status at diagnosis, even showing different immune response to treatment. These results reinforce the different biology behind CPR and non-CPR responses.

Chitosan Functionalized Magnetic Nanoparticles to Provide Neural Regeneration and Recovery after Experimental Model Induced Peripheral Nerve Injury.

(1) Background: Peripheral nerve injuries have a great impact on a patient's quality of life and a generally poor outcome regarding functional recovery. Lately, studies have focused on different types of nanoparticles and various natural substances for the treatment of peripheral nerve injuries. This is the case of chitosan, a natural compound from the crustaceans' exoskeleton. The present study proposes to combine chitosan benefic properties to the nanoparticles' ability to transport different substances to specific locations and evaluate the effects of magnetic nanoparticles functionalized with chitosan (CMNPs) on peripheral nerve injuries' rehabilitation by using an in vivo experimental model. (2) Methods: CMNPs treatment was administrated daily, orally, for 21 days to rats subjected to right sciatic nerve lesion and compared to the control group (no treatment) by analyzing the sciatic functional index, pain level, body weight, serum nerve growth factor levels and histology, TEM and EDX analysis at different times during the study. (3) Results: Animals treated with CMNPs had a statistically significant functional outcome compared to the control group regarding: sciatic functional index, pain-like behavior, total body weight, which were confirmed by the histological and TEM images. (4) Conclusions: The results of the study suggest that CMNPs appear to be a promising treatment method for peripheral nerve injuries.

Peripheral blood neurotrophic factor levels in children with autism spectrum disorder: a meta-analysis.

Increasing evidence suggests that abnormal regulation of neurotrophic factors is involved in the etiology and pathogenesis of Autism Spectrum Disorder (ASD). However, clinical data on neurotrophic factor levels in children with ASD were inconsistent. Therefore, we performed a systematic review of peripheral blood neurotrophic factors levels in children with ASD, and quantitatively summarized the clinical data of peripheral blood neurotrophic factors in ASD children and healthy controls. A systematic search of PubMed and Web of Science identified 31 studies with 2627 ASD children and 4418 healthy controls to be included in the meta-analysis. The results of random effect meta-analysis showed that the peripheral blood levels of brain-derived neurotrophic factor (Hedges' g = 0.302; 95% CI = 0.014 to 0.591; P = 0.040) , nerve growth factor (Hedges' g = 0.395; 95% CI = 0.104 to 0.686; P = 0.008) and vascular endothelial growth factor (VEGF) (Hedges' g = 0.097; 95% CI = 0.018 to 0.175; P = 0.016) in children with ASD were significantly higher than that of healthy controls, whereas blood neurotrophin-3 (Hedges' g = - 0.795; 95% CI = - 1.723 to 0.134; P = 0.093) and neurotrophin-4 (Hedges' g = 0.182; 95% CI = - 0.285 to 0.650; P = 0.445) levels did not show significant differences between cases and controls. Taken together, these results clarified circulating neurotrophic factor profile in children with ASD, strengthening clinical evidence of neurotrophic factor aberrations in children with ASD.

MiR-98-5p promotes ischemia/reperfusion-induced microvascular dysfunction by targeting NGF and is a potential biomarker for microvascular reperfusion.

OBJECTIVE: This study examined the correlation between serum miR-98-5p levels and indices of microvascular reperfusion in patients undergoing primary percutaneous coronary intervention (pPCI) after ST-segment elevation myocardial infarction (STEMI). Additionally, we evaluated the mechanisms by which miR-98-5p promoted ischemia/reperfusion (I/R)-induced injury in both cultured cell lines and an animal model. METHODS: Circulating miR-98-5p levels were measured and compared from 171 STEMI patients undergoing pPCI, who were divided into two groups: no-reflow and reflow. The levels of miR-98-5p, nerve growth factor (NGF), and transient receptor potential vanilloid 1 (TRPV1) were analyzed in cultured human coronary endothelial cells (HCECs) exposed to hypoxia/reoxygenation (H/R). The effects of antagomir-98-5p on myocardial I/R-induced microvascular dysfunction in vivo were evaluated. Target gene expression and activity were assessed. RESULTS: Higher miR-98-5p levels were associated with compromised indices of microvascular reperfusion. In vitro experiments on HCECs showed that exposure to H/R significantly increased miR-98-5p levels. We identified NGF as a novel target of miR-98-5p. Further, antagomir-98-5p relieved microvascular dysfunction and enhanced the expression of NGF and TRPV1 in the rat myocardial I/R model. CONCLUSIONS: MiR-98-5p promotes microvascular dysfunction by targeting the NGF-TRPV1 axis. Serum miR-98-5p serves as a potential biomarker for microvascular reperfusion.

Association between overactive bladder and serum nerve growth factor concentrations in women with high-grade uterine prolapse.

INTRODUCTION AND HYPOTHESIS: The association between overactive bladder (OAB) and uterine prolapse remains unclear. The extent of the role of serum nerve growth factor (NGF) levels in this relationship is also not known. Therefore, our study evaluated the association among OAB, high-grade uterine prolapse and serum NGF levels. METHODS: A total of 90 patients participated in our study and were grouped as follows. Group I included patients with high-grade uterine prolapse and OAB, group II included patients with only high-grade uterine prolapse, and group III included healthy women without uterine prolapse or OAB. Serum NGF level analysis was performed in all groups. RESULTS: Serum NGF levels varied greatly among the three groups, with significantly higher levels in group 1 than in groups 2 and 3 (p < 0.001). Serum NGF levels with a cutoff point of 120.49 pg/ml identified women with significant OAB symptoms to discriminate among groups with a sensitivity of 80%, specificity of 86.7%, positive predictive value of 75.0%, negative predictive value of 89.7% and positive likelihood ratio of 6.01 (p < 0.001). CONCLUSIONS: Our study showed that NGF-related pathways may play an active role in the pathophysiology of OAB with high-grade uterine prolapse patients based on obstruction hypothesis.

Nerve growth factor serum levels in treatment-resistant schizophrenic patients following electroconvulsive therapy.

BACKGROUND: Electroconvulsive Therapy (ECT) has been widely applied to treat schizophrenia (SCZ) in the presence of resistance to pharmacotherapy. The mechanism of action of ECT in schizophrenia has not been fully clarified, though its intrinsic mechanism presents analogies with some neurobiological processes mediated by nerve growth factor (NGF). OBJECTIVES: The aim of this study was to investigate in patients with treatment-resistant schizophrenia (TRS) the effect of ECT on acute and long-term NGF serum levels and the association with the clinical outcomes. METHODS: Twelve male inpatients with TRS underwent eight sessions of ECT. Blood samples were collected during the first and the eighth ECT at the following time points: 5 minutes before the induction of seizure and then at 0, 5, 15 and 30 minutes after seizure. RESULTS: Following ECT treatment, a substantial clinical improvement in symptom severity was indicated by a significant reduction in the Positive and Negative Syndrome Scale (PANSS) total and subscales scores. Even though the baseline NGF levels showed an increase over time, there were no statistical differences in NGF at time 0 at the first and the eighth ECT session. Furthermore, no correlation was observed between the severity of schizophrenic symptoms and NGF levels. CONCLUSIONS: This is the first study addressing peripheral NGF during ECT treatment in TRS, as well as the first study in which NGF has been evaluated in different ECT sessions at various time points. These findings may potentiate the knowledge about the neurotrophic effects of ECT and the role of NGF in synaptic plasticity related to possible mechanisms of schizophrenia treatment.

Value of peripheral neurotrophin levels for the diagnosis of depression and response to treatment: A systematic review and meta-analysis.

The neurotrophin hypothesis indicates that neurotrophic factors are important for the pathophysiology of major depressive disorder (MDD), with alterations in peripheral neurotrophin levels having potential clinical application for MDD. The present meta-analysis aimed to investigate the diagnostic value for MDD of peripheral neurotrophin levels in cross-sectional studies and the association between peripheral neurotrophin levels and the response to antidepressant treatment in longitudinal studies. Published studies in the PubMed and Web of Science databases were systematically searched up to February 2020. The search terms included depressive disorder, neurotrophic factor, serum/plasma and their synonyms. Human studies reporting on BDNF, GDNF, IGF-2, VEGF, NGF, FGF-2, and S100B levels in MDD patients were included. Data comparing MDD patients and healthy controls, and/or between responders and non-responders before and after antidepressant treatment were extracted. A random effects model was used to calculate standardized mean differences. A total of 177 original studies were identified, including 139 cross-sectional and 38 longitudinal studies. Significantly reduced BDNF and NGF levels and significantly elevated IGF-1, VEGF, and S100B levels were reported in MDD patients compared with healthy controls, while GDNF and FGF-2 levels were not significantly different. Furthermore, compared with non-responders, S100B levels at baseline and BDNF levels following treatment were significantly elevated in responders. In addition, there was a significantly elevated level of VEGF after treatment in responders only. In conclusions, alterations in peripheral neurotrophins levels were strongly associated with the biology and the treatment response of MDD. Further investigations are required to examine potential sources of heterogeneity.

Brain-derived neurotrophic factor and nerve growth factor concentrations in maternal and umbilical cord blood of opium-addicted mothers.

BACKGROUND: It is reported that opium consumption during pregnancy is associated with adverse pregnancy outcomes and neurodevelopmental defects in infants. BDNF and NGF alterations during pregnancy cause neurobehavioral deficits in the offspring. The aim of this study was to investigate the effect of opium addiction of pregnant women on BDNF and NGF levels in maternal and umbilical cord blood as well as pregnancy outcome. MATERIALS AND METHODS: The present research was a cross-sectional study. Thirty-five addicted pregnant women and 35 healthy pregnant women were included in the study. Blood samples were taken immediately after delivery from the maternal vein and umbilical cord. Then, BDNF and NGF concentrations in serum were measured by ELISA kits. The outcomes of pregnancy were determined by a checklist. Descriptive, t test, Mann-Whitney, and Chi-squared test were used to analyze the data. SPSS version 21 software was used for the analyses. A p-value <.05 was considered significant. RESULTS: BDNF levels were significantly lower in maternal and umbilical cord blood in the opium-addicted group (917.2 31 ± 316.5 and 784.6 ± 242.9 pg/ml, respectively) compared to the control group (1351 ± 375 and 1063 ± 341 pg/ml, respectively) (p < .0001 and p < .0002, respectively). Similarly, NGF level was significantly lower in maternal and umbilical cord blood in the opium-addicted group (302.7 ± 35.50 and 226.6 ± 45.43 pg/ml, respectively) compared to the control group (345.7 ± 43.16 and 251.2 ± 37.72 pg/ml, respectively) (p < .0001 and p = .0165, respectively). Adverse pregnancy outcomes such as NICU admissions, congenital anomalies, neonatal deaths, meconium contaminated amniotic fluid, respiratory problems, neonatal resuscitation, and low Apgar score were significantly higher in the opium-addicted group than in the control group. CONCLUSION: The results of this study revealed that opium consumption during pregnancy reduces BDNF and NGF levels in maternal and umbilical cord blood, which may cause neurodevelopmental disorders in later periods of infants' life.

Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study.

PURPOSE: The aim of the current study was to evaluate the effect of N-acetylcysteine (NAC) on the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients. METHOD: A prospective randomized controlled open label study was conducted on 75 breast cancer patients receiving adjuvant paclitaxel 80 mg/m2 weekly for 12 weeks. Eligible patients were randomized to either the low dose group; 1200 mg daily NAC, the high dose group; 1200 mg NAC twice daily or the control group; received paclitaxel only. The primary endpoint was the incidence of different grades of PIPN using National Cancer Institute's common toxicity criteria for adverse event (NCI-CTCAE) while secondary endpoints were the severity of PIPN using modified total neuropathy score (mTNS), quality of life (QOL) using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTX) subscale, serum nerve growth factor (NGF), and serum malondialdehyde (MDA). RESULTS: At the end of the 12-week period, the incidence of grade (2, 3) peripheral neuropathy was significantly lower in the high dose group (28.6%) compared to the low dose group (61.9%) and the control group (100%), p value < 0.001. A significant improvement in the mTNS and QOL scores was observed after 6 and 12 weeks in the high dose group and the low dose group compared to the control, p value < 0.001. Significantly higher levels of serum NGF in the high dose group and lower level of serum MDA in the high dose and the low dose group were observed. CONCLUSION: Oral NAC (1200 mg once and twice daily) might reduce the incidence and severity of PIPN and improve the patients' QOL. TRIAL REGISTRY: Clinical Trial.gov registration number: NCT03492047.

Different serum protein factor levels in first-episode drug-naive patients with schizophrenia characterized by positive and negative symptoms.

AIM: The clinical features of schizophrenia can be mainly divided into two symptom domains: positive and negative. Patients in each symptom domain respond differently to treatments, and their prognoses vary accordingly. Serum protein factors, such as nerve growth factor (NGF), neurotrophin-3 (NT-3), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), and the calcium-binding protein, S100ß, have been reported to be involved in the pathogenesis of schizophrenia. However, their roles in the positive and negative symptom domains have not been determined. In this study, we investigated whether the serum levels of these five protein factors differed among first-episode drug-naive schizophrenia patients in each symptom domain and in healthy controls. METHODS: Double-antibody sandwich ELISA were used to quantify the amounts of the five protein factors in serum. RESULTS: Compared with the levels in the controls (n = 60), increased serum levels of IL-6, IL-1ß, and S100ß and decreased serum levels of NGF and NT-3 were observed in first-episode drug-naive schizophrenia patients. Additionally, the serum levels of IL-6 and IL-1ß were significantly higher in schizophrenia patients characterized by negative symptoms (negative group, n = 37) than in those characterized by positive symptoms (positive group, n = 46). Based on multivariate regression analyses, serum levels of IL-1ß were positively associated with the Negative Symptom subscore of the Positive and Negative Syndrome Scale in the negative group and in all patients with schizophrenia. CONCLUSION: The two subtypes of schizophrenia may have different pathological mechanisms. Patients characterized by negative symptoms probably have more serious disturbances in neuroimmunology.

The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial.

Chronic hyperglycemia increases oxidative stress, activates inflammatory pathways and reduces nerve growth factor (NGF) among diabetic patients, which contribute to development of diabetic peripheral neuropathy (DPN). Tocotrienol-Rich Vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties which are postulated to target these pathogeneses in order to ameliorate DPN. This study aims to evaluate the effects of Tocovid on nerve conduction parameters and serum biomarkers among diabetic patients. This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on 80 eligible participants. The intervention group (n = 39) was randomly allocated to receive 200 mg of Tocovid twice a day, and the control group (n = 41) received placebo twice a day. At the end of eight weeks, the nerve conduction parameters, as assessed by nerve conduction study, as well as serum biomarkers (NGF, malondialdehyde, vascular cell adhesion molecule 1, tumor necrosis factor receptor 1 and thromboxane B2) were compared between the two groups. Compared to placebo, Tocovid significantly improves the nerve conduction velocities of all nerves (+1.25 m/s, interquartile range [IQR] 3.35, p < 0.001, median nerve; +1.60 m/s, IQR 1.80, p < 0.001, sural nerve; +0.75 m/s, IQR 2.25, p < 0.001, tibial nerve). Meanwhile, the levels of serum NGF were significantly higher in the Tocovid group as compared to placebo at eight weeks post-intervention. Participants receiving Tocovid illustrated highly significant improvement in terms of nerve conduction velocities for all nerves tested after eight weeks of supplementation. In addition, Tocovid supplementation elevated the levels of serum NGF, in which its increase is postulated to reflect enhanced neuronal functions. This novel finding suggests that Tocovid could be a disease-modifying agent targeting serum NGF to improve nerve conduction velocities.

Effects of hydrotherapy with massage on serum nerve growth factor concentrations and balance in middle aged diabetic neuropathy patients.

BACKGROUND: and purpose: Nerve growth factor (NGF) concentrations and balance are reduced in diabetic neuropathy (DN) patients. We examined the effects of hydrotherapy and massage on NGF, balance and glycemic markers in middle aged DN patients. MATERIALS AND METHODS: Patients were randomly assigned into four groups, aquatic exercise (AE; n = 10), AE + massage (AM; n = 10), massage (M; n = 10) or control (C; n = 9). Subjects in AE and AM groups exercised three times per week. Subjects in the AM and M groups received massage during the same period. Glycemic markers, NGF and balance were evaluated prior to and following the interventions. RESULTS: NGF, glycemic markers and dynamic balance improved in AE, AM and M groups; however, the increase was greater following the AM trial (p < 0.01) when compared to the other trials. CONCLUSION: A combination of hydrotherapy and massage enhances NGF concentrations, balance and the glycemic profile compared to hydrotherapy or massage alone.

Neuroinflammatory Markers in the Serum of Prepubertal Children with Down Syndrome.

Down Syndrome (DS) is the most common chromosomal disorder. Although DS individuals are mostly perceived as characterized by some distinct physical features, cognitive disabilities, and cardiac defects, they also show important dysregulations of immune functions. While critical information is available for adults with DS, little literature is available on the neuroinflammation in prepubertal DS children. We aimed to evaluate in prepubertal DS children the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), oxidative stress as free oxygen radicals defense (FORD), free oxygen radicals test (FORT), and cytokines playing key roles in neuroinflammation and oxidative processes as TNF-α, TGF-ß, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12. No differences were found in NGF between DS children and controls. However, BDNF was higher in DS subjects compared to controls. We also did not reveal changes in FORD and FORT. Quite interestingly, the serum of DS children disclosed a marked decrease in all analyzed cytokines with evident differences in serum cytokine presence between male and female DS children. In conclusion, the present study evidences in DS prepubertal children a disruption in the neurotrophins and immune system pathways.

The effect of combined scalp acupuncture and cognitive training in patients with stroke on cognitive and motor functions.

OBJECTIVE: To investigate the effect of combined scalp acupuncture and cognitive training on cognitive and motor functioning in patients with stroke during the recovery stage. METHODS: Seventy patients with post-stroke cognitive impairment were randomly divided into an experimental group and a control group. Patients in the experimental group additionally received scalp acupuncture and cognitive training, while the control group received sham scalp acupuncture and cognitive training. The cognitive and motor functioning of all patients were assessed using MMSE, LOTCA, and FMA, before and 12 weeks after treatment. In addition, the plasma BDNF and NGF levels were measured from peripheral blood samples using ELISA kits. RESULTS: After 12 weeks, the MMSE, LOTCA and FMA scores were significantly higher in the experimental group than in the control group. In the experimental group, there was an improvement in the total MMSE score, orientation, spatial executive function, the total LOTCA score, and the score of command of language orientation post-treatment. Significant improvements of BDNF and NGF were found in the experimental group after treatment, while only significant improvements of NGF was found in the control group after treatment. Both BDNF and NGF in the experiment group were higher than those in the control group at the last day of treatment. CONCLUSIONS: Combined scalp acupuncture and cognitive training can efficiently enhance cognitive and motor functions in patients with stroke during the recovery stage, which may be a more effective rehabilitation treatment after stroke than routine therapy and rehabilitation training alone.

Exploring the association between depression, suicidality and serum neurotrophin levels in adolescents.

Objective: The aim of this study was to identify potential differences in serum brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and neurotrophin-3 (NTF3) levels in adolescents with major depressive disorder (MDD) compared to healthy controls. The possible relationship between serum neurotrophin levels and suicidality in adolescents with MDD was also addressed.Methods: A total of 70 treatment-free adolescents with MDD and 40 healthy controls aged 11 to 19 years were enrolled. The severity of suicidality was determined using the Columbia-Suicide Severity Rating Scale, and the severity of depression and anxiety symptoms were evaluated by self-report inventories. Serum levels of neurotrophins were measured using an enzyme-linked immunosorbent assay.Results: The mean serum BDNF levels were significantly higher in adolescents with MDD than in control subjects; no significant difference was found between the groups for serum GDNF, NGF and NTF3 levels. No correlations were found between the levels of serum neurotrophins and the severity of depression or suicidality.Conclusions: The study results suggest that elevated serum BDNF levels may be related to MDD in adolescents. However, our findings did not support a role for neurotrophins in suicidality.Key pointsSerum BDNF levels were higher in adolescents with MDD than in controls.No significant alterations of serum levels of GDNF, NGF and NTF3 were evident in adolescents with MDD.Neurotrophin levels were not associated with suicidal ideation and behaviours.