Nerve Growth Factor Levels Research Articles

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.

Effects of far infrared light on Alzheimer's disease-transgenic mice.

Far infrared light has been used in many medical procedures. However, the detailed biological mechanisms of infrared light’s effects have not yet been elucidated. Many researchers have pointed out the thermal effects of treatments such as infrared saunas, which are known to increase blood flow. Alzheimer’s disease (AD) is associated with gradual decreases in brain blood flow and resulting dementia. In this study, we attempted to clarify the beneficial effects of far infrared light using the 5xFAD mouse, a transgenic model of AD. We exposed 5xFAD mice to far infrared light for 5 months. Among the far infrared-exposed AD mice, body weights were significantly decreased, and the levels of nerve growth factor and brain-derived neurotrophic factor protein were significantly increased in selected brain areas (compared to those in non-irradiated AD mice). However, cognition and motor function (as assessed by Morris water maze and Rota Rod tests, respectively) did not differ significantly between the irradiated and non-irradiated AD mouse groups. These results indicated that exposure to far infrared light may have beneficial biological effects in AD mice. However, the experimental schedule and methods may need to be modified to obtain clearer results.

Effects of different implant surface properties on the biological behavior of Schwann cells.

This study investigated the effects of different implant surface properties on the biological behavior of Schwann cells. Schwann cells (SCs) were cultured on three types of implant surfaces including smooth polished (SMO), sand-blasted, large grit, acid-etched (SLA), and chemically-modified SLA (modSLA). At different time points, the morphology and adhesion of SCs on the implant surfaces were observed by scanning electron microscope. Cell proliferation activity was detected by MTT method. The expression levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were detected by enzyme-linked immunosorbent assay. Changes in the mRNA levels of NGF and BDNF were detected by real-time fluorescent quantitative polymerase chain reaction (PCR). SCs adhered, stretched, and proliferated well on the three types of implant surfaces. On the 3rd, 5th, and 7th days, the OD values of the SMO group were higher than those of the SLA group and the modSLA group, and the difference was statistically significant (P<0.05). On the 3rd day, the expression and mRNA levels of NGF and BDNF in the SLA group and the modSLA group were higher than those in the SMO group (P<0.05); in particular, the levels in the modSLA group were higher than those in the SLA group (P<0.05). Different implant surface properties have different effects on the biological behavior of SCs. Proliferation of SCs is significantly promoted by smooth surface, while secretion and gene expression of neurotrophic factors are significantly promoted by modSLA surface at early stage.

Taurine Alleviates Sympathetic Innervation by Inhibiting NLRP3 Inflammasome in Postinfarcted Rats.

The NLRP3 inflammasome is activated by myocardial infarction and then induces the activation of inflammatory caspase-1 activation and maturation of IL-1β, a regulator of synthesis of the nerve growth factor (NGF). Here, we studied whether taurine, 2-aminoethanesulphonic acid, can attenuate cardiac sympathetic reinnervation by modulating NLRP3 inflammasome-mediated NGF in a rat model of myocardial infarction. Male Wistar rats were subjected to coronary ligation and then randomized to either saline or taurine for 3 days or 4 weeks. Postinfarction was associated with activation of NF-κB (p65) and NLRP3 inflammasome component and increased the protein and expression of IL-1β. Macrophages at the border zone were shown to be positive for IL-1β 3 days postinfarction. Compared with vehicle, infarcted rats treated with taurine significantly attenuated myocardial messenger RNA and protein levels of NF-κB, NLRP3 inflammasome, mature caspase-1, and IL-1β. Immunofluorescent analysis, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting of NGF showed that sympathetic hyperinnervation was blunted after administering taurine. Arrhythmia vulnerability in the taurine-treated infarcted rats was significantly improved than those in vehicle. Ex vivo studies showed that taurine infusion reduced myocardial IL-1β level at the extent similar to either pyrrolidine dithiocarbamate or CP-456,773, inhibitors of NF-κB and NLRP3 inflammasome, implying the key axis of NF-κB/NLRP3 inflammasome in mediating taurine-related anti-inflammation. Furthermore, administration of anti-IL-1β antibody reduced NGF levels. Taurine attenuated sympathetic innervation mainly by NLRP3 inflammasome/IL-1β-dependent pathway, which downregulated expression of NGF in infarcted rats. These findings may provide a new insight into the anti-inflammation effect of taurine.

Correlation between the NGF levels and questionnaire forms in patients receiving antimuscarinic treatment and those receiving onabotulinum toxin-A injection.

To compare nerve growth factor (NGF) levels in patients who received antimuscarinic, versus onabotulinum toxin-A (onaBoNT-A) injection, as well as to investigate whether there is a correlation between NGF levels, and 8-item overactive bladder questionnaire(OAB-V8), urogenital distress inventory (UDI)-6, and incontinence impact questionnaire (IIQ)-7 forms. Fourty adult patients with OAB were enrolled in this prospective study. An antimuscarinic was prescribed to 20 naive patients, and onaBoNT-A injection was administered to 20 patients, who were refractory to antimuscarinics. Urine samples were obtained before, and after 3rd and 6th months of treatment, and NGF levels were measured. Symptom scores of OAB-V8, UDI-6,and IIQ-7 were recorded. There was no significant difference between groups in terms of the initial OAB-V8, IIQ-7, and UDI-6 scores, whereas NGF values showed no significant difference over time in onaBoNT-A group (p=0.069, p=0.069). NGF levels were significantly lower in 3rd and 6th months, in patients receiving antimuscarinic (p=0.003, p=0.007); a strong correlation was found in 3rd month between the NGF levels, OAB-V8 scores (r=0.704, p=0.001), and IIQ-7 scores (r=0.676, p=0.001), and a moderate correlation between NGF levels, and UDI-6 scores (r=0.583, p=0.007). In the 6th months, a very strong correlation was found between NGF levels, and OAB-V8 scores (r=0.811, p=0.004), and a strong correlation was found between NGF levels, and IIQ-7 scores (r=0.671, p=0.001). In onaBoNT-A group, there was no significant correlation between NGF levels, and other variables. NGF level might be a good marker to evaluate effectiveness of treatment in patients receiving antimuscarinics, owing to correlation of urinary NGF levels with symptom scores. Lack of correlation in patients receiving onaBoNT-A injection could be a result of differences in the mechanism of action.

Long term neuroprotective effects of acute single dose MK-801treatment against traumatic brain injury in immature rats

Because brain development continues during adolescence, childhood trauma is a major health problem in pediatric ages. It is known traumatic brain injury (TBI) results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. The study aims to investigate the long-term effects of MK-801 (dizocilpine), an N-methyl d-aspartate (NMDA) receptor antagonist, on hippocampal damage, locomotor activity, and cognitive functions following TBI in immature rats. MK-801 (1 mg/kg) was injected intraperitoneally immediately after TBI. Thirty-seven litters were randomly allocated into three groups at 7 days (P7) of postnatal age: a control group, a trauma group, and an MK-801 treatment group. The control group received no treatment; the trauma group received saline as vehicle control for the MK-801 group and the MK-801 group received a single dose of 1 mg/kg MK-801 immediately after TBI. Hippocampal damage was examined by Hematoxylin-Eosin staining. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), NMDA-R, and glial fibrillar acidic protein (GFAP) immunohistochemistry and, BDNF, NGF, and NMDA-R ELISA protein levels were evaluated 125 days after trauma. Histopathological and immunohistochemical evaluations showed that treatment with MK-801 significantly ameliorated the trauma-induced hippocampal neuron loss and increased BDNF, NGF, NMDA-R, GFAP expressions in CA1, CA3, and DG hippocampal regions. Additionally, treatment with MK-801 decreased anxiety and increased hippocampus-dependent memory of animals subjected to brain injury after TBI. These results show that acute treatment of MK-801 has a neuroprotective role against trauma-induced hippocampal neuron loss and associated cognitive impairment in rats.

Relationship of potential biomarkers of interstitial cystitis/painful bladder syndrome

BACKGROUND: Biomarker identification fulfills the need for simple, accurate, and non-invasive diagnostic methods for interstitial cystitis/painful bladder syndrome (IC/PBS). The simultaneous study of cytokines and growth factors is essential for understanding the role of biomarkers.&#x0D; AIM: This work determines the concentration of interleukins (IL) 6 and 8, nerve growth factor (NGF), heparin-binding epidermal growth factor (HB-EGF), and their relationship in patients with IC/PBS.&#x0D; MATERIALS AND METHODS: This study examined 126 female patients with IC/PBS, with a mean age of 46.714.0 years. The disease duration averaged 6.02.8 years. The control group consisted of 20 women without IC/PBS, with a mean age of 35.39.7 years. The level of IL-6 and IL-8 in blood serum and urine was determined by ELISA. The NGF and HB-EGF levels were determined by ELISA using the appropriate test kits. Statistical analysis was performed using SPSS software version 15.0. The Students t-test and Spearmans correlation coefficient were calculated.&#x0D; RESULTS: In patients with IC/PBS, blood levels of IL-6 and IL-8 exceeded the control indicator by 65.99% (t=4.62, p=0.000) and by 67.14% (t=2.81, p=0.006), respectively, the NGF level exceeded it by 8.82% (t=0.10, p=0.920), and the HB-EGF level decreased by 30.84% (t=0.62, p=0.537). In urine, the level of IL-6 in IC/PBS was increased by 52.94% (t=7.62, p=0.000), IL-8 level was increased by 57.53% (t=2.01, p=0.049), NGF was increased by 50.44% (t=2.06, p=0.043), and HB-EGF level was increased by 56.44% (t=2.01, p=0.049). Cytokines correlated with growth factors with weakly bound in blood and urine (p 0.05). A strong, direct relationship was registered between the urine levels of NGF and HB-EGF (r=+0.987, p 0.05).&#x0D; CONCLUSIONS: Correlations between IL-6 and IL-8 with NGF and HB-EGF in urine indicate an increased risk of damage to the bladder epithelium. The increase in urinary HB-EGF is a response to a significant increase in urinary NGF and may be a bladder epithelial defense mechanism.

Effect of neural therapy on NGF and BDNF serum levels in patients with chronic pain. A pilot study

Introduction: Neurotrophins (NT) are a family of proteins consisting of the nerve growth factor (NGF), the brain-derived neurotrophic factor (BDNF) and NT-3 and NT-4/5. These proteins play an essential role in neuronal survival, differentiation, and proliferation. Objectives: To analyze the variations of NGF and BDNF serum levels in patients with chronic pain after undergoing neural therapy and to establish the effects of this type of intervention on their quality of life. Materials and methods: Prospective pilot study conducted in 10 patients with chronic pain treated with neural therapy between July 2017 and April 2018 in Bogotá D.C., Colombia. Three consultations were performed (one in which the intervention was initiated, and two follow-up visits every three weeks). During each consultation, the patients’ quality of life was assessed using the SF-12 scale and their NGF and BDNF serum levels were measured. Data were analyzed by means of descriptive statistics, using medians and interquartile ranges for quantitative variables, and absolute frequencies and percentages for qualitative variables. Results: The median score on the SF-12 scale tended to improve in the first and second follow-up visits compared with the baseline score (pre-intervention), particularly during the first follow-up visit (consultation No. 1: 34.5; follow-up No. 1: 39.5, and follow-up No. 2: 38). Median NGF serum levels had a downward trend after the intervention, particularly in the first follow-up visit (157.6, 42.95, and 237.8, respectively), and in the case of BNDF, an overall downward trend was also found (29.96, 19.24 and 20.43, respectively). An improvement in quality of life related to the decrease in the serum levels of both neurotrophins was observed. Conclusion: Neural therapy intervention reduced NGF and BDNF serum levels and improved the quality of life of the participants. Therefore, the behavior of these neurotrophins could become a biomarker for the diagnosis, treatment, and follow-up of patients with chronic pain.

Circulating NGF is correlated with indexes of diabetes progression and P2X 3 expression in UCD‐T2DM rats

Type 2 diabetes is associated with neuropathic symptoms, including development of peripheral neuropathy and an exaggerated exercise pressor reflex, both of which have been demonstrated in UC Davis Type 2 diabetes mellitus (UCD-T2DM) rats. This novel animal model more closely mimics the human disease state than traditional T2DM rodent models. Several studies have demonstrated changes in nerve growth factor (NGF) in diabetic patients, with some showing increases and others decreases, and this has been proposed as a potential driver of the development of peripheral neuropathy. Additionally, increased expression of purinergic 2X3 (P2X3) receptors has been suggested as a potential mechanism underlying peripheral nerve sensitization. However, interactions between these factors during diabetes progression are not fully understood. Therefore, the objective of this study was to investigate the relations between NGF, P2X3, and peripheral neuropathy during diabetes progression in UCD-T2DM rats. We hypothesized that NGF levels would be correlated with traditional indexes of diabetes (glucose and HbA1c) as well as P2X3 expression and mechanical allodynia as measured by paw withdrawal threshold. Methods Blood was collected monthly from the tail vein of male UCD-T2DM rats from 4 to 8 months of age. Serum levels of NGF, leptin, and insulin were measured by ELISA. Development of mechanical allodynia was tracked monthly using Von Frey filaments to measure paw withdrawal threshold. At 8 months of age, L4-5 dorsal root ganglia were harvested and P2X3 receptor protein levels were quantified using the Jess automated western blotting platform. Pearson correlations were calculated using Graphpad Prism 9. Results Consistent with wasting and loss of pancreatic beta cell function during diabetes progression, glucose and HbA1c increased significantly over time whereas body weight, insulin, and leptin levels decreased. Circulating NGF concentration was negatively correlated with glucose (r=-0.61, P<0.01) and HbA1c (r=-0.79, p<0.01) demonstrating that NGF decreased with the progression of diabetes. Circulating NGF concentration was positively correlated with body weight (r=0.61, p<0.01), insulin (r=0.77, p<0.01), and leptin (r=0.82, p<0.01) thereby showing the same decreasing trend with diabetes progression. Interestingly, NGF was negatively correlated with P2X3 receptor expression (r=-0.81, p=0.03) and neither NGF nor P2X3 were significantly associated with mechanical allodynia (NGF: r=0.14, p=0.45; P2X3: r= 0.15, p=0.75). Conclusion Circulating NGF is significantly associated with several indexes of diabetes progression in UCD-T2DM rats, including glucose, HbA1c, leptin, and insulin levels. Though decreasing concentrations of NGF are associated with increases in P2X3 receptor protein expression, neither NGF nor P2X3 appear to be associated with the development of mechanical allodynia.

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.

Diagnostic value of nerve growth factor in detrusor overactivity: a study on women with mixed urinary incontinence.

Urinary incontinence has a profound impact on women's quality of life. Studies have shown that changes in urinary protein levels could be a potential diagnostic biomarker in some urological diseases. The aim of present study is to determine the diagnostic value of nerve growth factor (NGF) in women with mixed urinary incontinence (MUI) as a diagnostic biomarkers of detrusor overactivity (DO). Seventy women aged between 20 and 75years with MUI were enrolled in this prospective study. All participants underwent urodynamic study. Urine NGF levels were measured using an ELISA method. NGF level was compared between groups using Mann-Whitney U test. Receiver Operator Characteristic (ROC) analysis was employed to evaluate the diagnostic performance of urinary NGF. The results showed that the median (min, max) of NGF in patients with DO was significantly higher in comparing to its level in women without DO [184.10 (31, 346.60) pg/ml vs. 151.80 (21, 210.70)], respectively (P = 0.035). Using receiver-operator characteristics analysis, the threshold urinary NGF value of 102.00pg/ml provided a sensitivity of 88% and specificity of 40% in diagnosing DO, PPV of 39.1%, and NPV of 88.2%, positive likelihood ratio 2.18 and negative likelihood ratio of 0.45 (P = 0.02). Based on high sensitivity and low specificity, we can conclude that NGF can be a good tool for ruling out the OAB when the test is negative. However, the future investigations are needed to expand the observed correlation in larger groups of women with DO.

EFFECT OF GLYPROLINES ON THE LEVEL OF NERVE GROWTH FACTOR UNDER CONDITIONS OF "SOCIAL" STRESS

Today a study aimed at the role of various neurotrophic factors in the implementation of a stress response and their influence on the functioning of the central and peripheral nervous system is of particular interest. Nerve growth factor (NGF) which belongs to a special group of polypeptide regulators has the most expressed neurospecificity. It has been established that this factor has a neuroprotective effect which is realized due to its ability to induce the induction of antiapoptotic proteins and inhibition of proapoptotic ones, thereby affecting the survival rate, as well as the differentiation of individual populations of peripheral neurons. Currently neuropeptide drugs with a wide spectrum of biological activity are considered as the leading stress protectors. Glyproline neuropeptides with proven versatile pharmacological activity, namely neuroprotective, anti-inflammatory, regenerative, immunotropic, etc., attract particular attention. Objective: to study the effect of glyprolines on the level of nerve growth (NGF) in the blood serum of white rats under conditions of "social" stress. Materials and methods. The study was carried out on 90 white non-linear male rats for 6 months. The experimental model of "social" stress was formed as a result of sensory contact for 20 days, followed by the formation of aggressive and submissive types of behavior. Glyproline compounds Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank), Pro-Gly-Pro and Pro-Gly-Pro-Leu were injected intraperitoneally at a dose of 100 pg/kg/day from the 1st day of stress exposure by the course 20 days. The level of NGF in the blood serum of white rats was assessed by the enzyme-linked immunosorbent assay using an ELISA Kit for NGF (USA). Results. Exposure to "social stress" led to a decrease in the level of nerve growth factor which probably has a cause-and-effect relationship with a decrease in neurogenetic processes. The observed restoration of the NGF level under the influence of glyprolines Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank), Pro-Gly-Pro and Pro-Gly-Pro-Leu indicates their stress and neuroprotective activity.

Placental neurotrophin levels in gestational diabetes mellitus.

Neurotrophins are known to influence the development and maturation of the feto-placental unit and affect fetal growth trajectories. This study reports the levels of nerve growth factor (NGF) and brain-derived growth factor (BDNF) in the placenta of women with gestational diabetes mellitus (GDM). A total number of 60 women with GDM and 70 women without GDM (non-GDM) were included in the study. Placental NGF and BDNF levels were measured using commercially available ELISA kits. Placental NGF levels were lower (p<.05) in women with GDM compared to non-GDM women. Maternal body mass index (BMI), mode of delivery, and the gender of the baby influenced the placental NGF levels. Placental BDNF levels were similar in GDM and non-GDM women. There was an influence of baby gender on the placental BDNF levels while maternal BMI and mode of delivery did not show any effect. In regression models adjusted for maternal age at delivery, gestational age, maternal BMI, mode of delivery, and baby gender, the placental NGF levels in the GDM group were lower (-0.144pg/ml [95% CI -0.273, 22120.016] p=.028) as compared to the non-GDM group. However, there was no difference in the BDNF levels between the groups. This study for the first time demonstrates differential effects on neurotrophic factors such as BDNF and NGF in the placenta in pregnancies complicated by GDM. Alterations in the levels of placental neurotrophins in GDM deliveries may affect placental development and fetal brain growth. This has implications for increased risk for neurodevelopmental pathologies in later life.

Estrogen Regulation of the Expression of Pain Factor NGF in Rat Chondrocytes.

ObjectivePain is the main symptom of osteoarthritis (OA). Nerve growth factor (NGF) plays a crucial role in the generation of OA pain. And estrogen-alone used resulted in a sustained joint pain reduction in postmenopausal women. So we aim to find whether estrogen alters chondrocytes’ NGF level, affecting OA pain.MethodsPrimary chondrocytes and cartilage explants isolated from Sprague Dawley rat knees were cultured with physiological concentrations of estrogen (17β-Estradiol ≥ 98%, E2), Estrogen Receptor α (ERα) inhibitor and stimulants. Then, chondrocytes NGF mRNA expression and protein release were analyzed by a quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) respectively. Additionally, cultures were pre-incubated with MEK-ERK inhibitor to identify the signaling pathway that estrogen alters NGF mRNA and protein levels.ResultsWe found that chondrocytes NGF expression and release were decreased by E2. E2 also reduced chondrocytes IL-1β-stimulated or TGF-β1-stimulated NGF expression. Phosphorylated extracellular signal-regulated kinasep1/2 (p-ERK1/2) signals were detected stronger than the control group by Western Blotting (WB). When we cultured chondrocytes with PD98059 (MEK-ERK inhibitor, PD), NGF mRNA expression was added to 1.41Ct (2.07±0.1 fold).ConclusionWe showed that E2 reduces chondrocytes NGF expression significantly, even after stimulation by TGF-β1 or IL-1β. MEK-ERK signaling is involved in this process.

The Lucerne Protocol for the Production of Autologous Serum Eyedrops.

There are a variety of protocols for manufacturing autologous serum (AS) eye drops. The Lucerne protocol for the production of AS eye drops uses a slightly reduced gravitational (g)-force and time for the centrifugation process (2500 × g for 10 minutes), compared to previously published optimised protocols, to obtain high levels of epitheliotropic growth factors (3000 × g for 15 minutes). The goal of this study was to compare the concentrations of growth factors, albumin and lysozyme in autologous serum eye drops manufactured with these protocols. Blood from 5 healthy volunteers was placed in plastic tubes without an anticoagulant. Tubes from each donor were left in a vertical position for 2 hours at room temperature to facilitate coagulation, followed by centrifugation at either 2500 × g for 10 minutes or at 3000 × g for 15minutes at room temperature. The serum levels of beta nerve growth factor (β-NGF), transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A) were measured in triplicate with a multi-analyte Simple Plex platform. The Simple Plex cartridge allows each sample to be run in triplicate for each analyte and prevents any interaction between the antibody components for each biomarker. The serum level of albumin was measured by turbidimetric immunoassay Tina-quant and of lysozyme by single radial immunodiffusion assay. For all analytes, the reduced g-force and centrifugation time did not result in a significant difference in serum levels. The Lucerne protocol for the production of autologous serum eye drops with reduced g-force and a shorter centrifugation time does not affect the concentrations of the main epitheliotropic growth factors, albumin and lysozyme, in AS eye drops.

Sulfated Polysaccharide Isolated from the Nacre of Pearl Oyster Improves Scopolamine-Induced Memory Impairment.

Pearl and nacre have been used in traditional medicines for treating brain dysfunctions, such as epilepsy, myopia, palpitations and convulsions. We previously showed that a pearl oyster nacre extract improves scopolamine-induced memory impairments using the Y-maze, Banes maze and object recognition tests. In this study, we aimed to isolate the memory-improving substance using ion-exchange column chromatography and reverse-phase column chromatography and elucidate the molecular mechanism underlying its memory-improving activity. The isolated substance was found to be a sulfated polysaccharide with a molecular weight of approximately 750 kDa. Monosaccharide composition analysis showed that it was rich in galactose, glucose, mannose and uronic acid. Furthermore, the mRNA expression levels of oxidative stress, inflammatory response and neuroprotective factors in the cerebral cortex were investigated. Treatment with the polysaccharide increased the expression levels of the antioxidant enzymes Cu, Zn -superoxide dismutase (SOD) and catalase and attenuated the scopolamine-mediated upregulation of the inflammatory cytokines interleukin-1 and interleukin-6. In addition, the polysaccharide suppressed the decrease in the expression levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These findings strongly suggest that the polysaccharide in the nacre extract mediated its antiamnesic effects by preventing oxidative stress and inflammation and increasing the expression levels of BDNF and NGF.

Relationship of Pain Catastrophizing With Urinary Biomarkers in Women With Bladder Pain Syndrome.

Brain-derived neurotrophic factor (BDNF) has been implicated in central neurological processes. We hypothesize that greater pain catastrophizing is associated with higher urinary BDNF levels in women with bladder pain syndrome. A secondary analysis of a database of women with urinary urgency was conducted. We identified women who met AUA criteria of bladder pain syndrome. Urinary symptoms, pain catastrophizing, and neuropathic pain were measured using the Female Genitourinary Pain Index, Pain Catastrophizing Scale and painDETECT questionnaires respectively. The relationship of the catastrophizing score with urinary BDNF (primary outcome) and other urinary biomarkers, including nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and osteopontin, was evaluated using univariable and multivariable analyses. In 62 women with bladder pain syndrome, 15 (24%) reported pain catastrophizing symptoms (Pain Catastrophizing Scale score >30). Higher catastrophizing scores were associated with worse urinary symptoms, greater pelvic pain, greater neuropathic pain, and worse quality of life scores (all P < 0.01). On multivariable analysis, after controlling for age, body mass index and urinary symptoms, a higher pain catastrophizing score was associated with lower BDNF (P = 0.04) and lower VEGF levels (P = 0.03). Urinary urgency was associated with a higher NGF level (P = 0.04) while bladder pain was associated with higher levels of NGF (P = 0.03) and VEGF (P = 0.01). Neuroinflammatory mechanisms contribute to the central processing of pain in women with bladder pain syndrome. Worse urinary symptoms are associated with higher NGF and VEGF levels, but worse pain catastrophizing is associated with lower BDNF and VEGF levels. Urinary BDNF levels may be useful in phenotyping women who have central augmentation of pain processing.

Caffeine improves bladder function in diabetic rats via a neuroprotective effect.

Diabetic cystopathy (DCP) is one of the most common complications of diabetes mellitus (DM). A previous study reported that caffeine may improve bladder dysfunction in rats with DM. The aim of the present study was to investigate the mechanisms behind the capacity for caffeine to improve bladder function in rats with DM. Sprague Dawley rats were divided into four groups: control, caffeine, DM and DM plus caffeine treatment (DM + caffeine). Bladder function was measured by urodynamic analyses. The levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP) in the bladder tissue were detected by ELISA. Apoptosis in the dorsal root ganglion (DRG) was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, cleaved caspase-3, caspase-9 and cleaved caspase-9 proteins in the DRG were detected by western blotting. Following treatment with caffeine, the urination time and micturition interval of rats with DM were improved, the bladder wet weight was decreased, and the maximum voiding pressure was increased. Relative to that in the DM group, the expression levels of NGF, BDNF and CGRP in the bladder tissue of DM + caffeine rats increased; cellular apoptosis in the DRG of DM + caffeine rates decreased; and the expression levels of Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 proteins in the DRG of DM + caffeine rats were restored to a certain extent. In conclusion, caffeine promotes bladder function in rats with DM through a protective effect on DRG.

Comparison of the Therapeutic Effects of Sodium Valproate and Levetiracetam on Pediatric Epilepsy and the Effects of Nerve Growth Factor and γ-Aminobutyric Acid.

Background:We aimed to investigate the therapeutic effect of sodium valproate combined with levetiracetam on pediatric epilepsy and the effects of nerve growth factor and γ-aminobutyric acid.Methods:Eighty-three epileptic children admitted to Xuzhou Municipal Hospital of Xuzhou Medical University (Xuzhou, China) from Jan 2018 to Nov 2019 were collected and divided into a control group (40 cases, treated with sodium valproate alone) and an observation group (43 cases, treated with sodium valproate combined with levetiracetam). The therapeutic effect and incidence of adverse reactions were observed. The levels of nerve growth factor (NGF), γ-aminobutyric acid (GABA) and serum neuron-specific enolase (NSE) of children were compared. Changes of cognitive function and the total effective rate were evaluated. Logistic regression analysis was used to analyze the risk factors affecting the therapeutic effect.Results:After treatment, NGF, GABA and NSE in the observation group were significantly improved compared with those before treatment. The cognitive function of the observation group was significantly improved after treatment when compared with the control group. The total effective rate in the observation group was higher than that in the control group. Adverse reactions in the observation group were less than those in the control group. Seizure type, NGF, GABA, NSE and treatment methods were independent risk factors affecting the therapeutic effect of pediatric epilepsy.Conclusion:The application of sodium valproate combined with levetiracetam in the treatment of pediatric epilepsy is helpful to improve the overall therapeutic effect, significantly improve the cognitive function of children, and improve the levels of NGF, GABA and NSE.

Effects of combination treatment with transcranial magnetic stimulation and bone marrow mesenchymal stem cell transplantation or Raf inhibition on spinal cord injury in rats.

Spinal cord injury (SCI) remains a global challenge due to limited treatment strategies. Transcranial magnetic stimulation (TMS), bone marrow mesenchymal stem cell (BMSC) transplantation and downregulation of Raf/MEK/ERK signaling effectively improve SCI. The combination of BMSCs and TMS displays synergistic effects on vascular dementia. However, whether TMS displays a synergistic effect when combined with BMSC transplantation or Raf inhibitor (RafI) therapy for the treatment of SCI is not completely understood. The present study aimed to compare the therapeutic effect of monotherapy and combination therapy on SCI. In the present study, 8-week-old female Sprague Dawley rats were used to establish a model of SCI using the weight-drop method followed by treatment with monotherapy (TMS, BMSCs or RafI) or combination therapy (TMS+BMSCs or TMS+RafI). The effect of monotherapy and combination therapy on locomotor function, pathological alterations, neuronal apoptosis and expression of axonal regeneration-associated factors and Raf/MEK/ERK signaling-associated proteins in the spinal cord was analyzed by Basso, Beattie and Bresnahan (BBB) scoring, hematoxylin and eosin staining, TUNEL-neuronal nuclei (NeuN) staining and immunofluorescence or western blotting, respectively. The results demonstrated that compared with untreated SCI model rats, monotherapy significantly enhanced locomotor functional recovery, as evidenced by higher BBB scores, and slightly alleviated histopathological lesions of the spinal cord in SCI model rats. Furthermore, monotherapy markedly suppressed neuronal apoptosis and promoted axonal regeneration, as well as inhibiting astroglial activation in SCI model rats. The aforementioned results were demonstrated by significantly decreased numbers of apoptotic neurons, markedly decreased expression levels of glial fibrillary acidic protein (GFAP), significantly increased numbers of NeuN+ cells, markedly increased expression levels of growth-associated protein 43 (GAP-43) and significantly upregulated nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) expression levels in monotherapy groups (excluding the RafI monotherapy group) compared with untreated SCI model rats. In addition, monotherapy markedly suppressed activation of the Raf/MEK/ERK signaling pathway, as evidenced by significantly reduced p-Raf/Raf, p-MEK/MEK and p-ERK/ERK protein expression levels in monotherapy groups (excluding the BMSC monotherapy group) compared with untreated SCI model rats. Notably, combination therapy further alleviated SCI-induced spinal cord lesions and neuronal apoptosis, increased GAP-43, NGF and BDNF expression levels, downregulated GFAP expression levels and inhibited activation of the Raf/MEK/ERK signaling pathway in SCI model rats compared with the corresponding monotherapy groups. Therefore, it was hypothesized that compared with monotherapy, combination therapy displayed an improved therapeutic effect on SCI by further suppressing Raf/MEK/ERK signaling. The results of the present study provided an important basis for the clinical application of combination therapy.