Tissue Engineering Scaffold Slowly Releasing Neurotrophic Factors to Bridge Long Peripheral Nerve Defect

Consistent application of neurotropic factors is necessary in peripheral nerve regeneration, yet challenging to achieve. Here we used a novel neurotropic factor controlled release system consisted of fibrin, fibronectin and hydrogel to slowly release two neurotrophic factors. At the same time, physiological saline and reverse nerve suturing were used as negative and positive control. A year after surgery, animals which were treated by neurotrophic factor slow release system achieved far better neural regeneration and myelination, as well as superior recovery of hindfoot than the negative control group. In the meanwhile, the results in the experimental group are still inferior to the nerve allograft group. In can be concluded from those results that, consistent releasing of neurotrophic factors can significantly promote long peripheral nerve regeneration, but still short of achieving the results same as the gold standard of autologous nerve grafting.

Influence of N-Arachidonoyl Dopamine and N-Docosahexaenoyl Dopamine on the Expression of Neurotrophic Factors in Neuronal Differentiated Cultures of Human Induced Pluripotent Stem Cells under Conditions of Oxidative Stress

Oxidative stress (OS) is implicated in the pathogenesis of several neurodegenerative diseases. We have previously shown that N-acyl dopamines (N-ADA and N-DDA) protect the neural cells of healthy donors and patients with Parkinson’s disease from OS. In this study, we assessed the effects of N-acyl dopamines on the expression of neurotrophic factors in human-induced pluripotent stem cell-derived neuronal cultures enriched with dopaminergic neurons under conditions of OS induced by hydrogen peroxide. We showed that hydrogen peroxide treatment increased BDNF but not GDNF mRNA levels, while it did not affect the secretion of corresponding proteins into the culture medium of these cells. Application of N-acyl dopamines promoted BDNF release into the culture medium. Under conditions of OS, N-DDA also increased TRKB, TRKC and RET mRNA levels. Furthermore, N-acyl dopamines prevented cell death 24 h after OS induction and promoted the expression of antioxidant enzymes GPX1, GPX7, SOD1, SOD2 and CAT, as well as reduced the BAX/BCL2 mRNA ratio. These findings indicate that stimulation of the expression of neurotrophic factors and their receptors may underlie the neuroprotective effects of N-acyl dopamines in human neurons.

Plasma levels of neurotrophic factors are not associated with the severity of depression

Depression is one of the most common mental illnesses. Impaired neurogenesis is observed in depression. Studying the concentration of biochemical indicators in the blood that may be involved in the pathogenesis of depression, looking for associations with the severity of depressive symptoms can be useful as an objective diagnosis of the disease and predicting the severity of the pathology. We determined plasma concentrations of the monoamine neurotransmitters serotonin and dopamine, and neurotrophic factors involved in neurogenesis (BDNF, CDNF and neuropeptide Y) in depressed patients and healthy volunteers with the same socio-demographic parameters using enzyme immunoassay and mass spectrometry. All study participants were administered the Hamilton Depression Scale (HAMD), the Generalized Anxiety Disorder Questionnaire (GAD-7), and the Center for Epidemiological Studies (CES-D). The cumulative scores on the three scales examined were significantly higher in depressed patients than in controls. The concentration of serotonin, dopamine, BDNF, CDNF, and neuropeptide Y in plasma did not differ between the subject groups and was not associated with the scores on the scales. Positive correlations were found between the content of neuropeptide Y and serotonin, BDNF and CDNF in blood plasma. Thus, although these markers are related to the pathophysiology of depression, they do not correlate with the severity of symptomatology and possibly in plasma cannot reflect processes occurring in the brain.

Features and patterns of changes in neurochemical parameters at different stages of chronic mercury intoxication

Introduction. At present, the features of the clinical picture and pathogenesis of the formation and progression of chronic intoxication under the influence of mercury remain insufficiently studied. Purpose. To study the features and patterns of changes in the neurotransmitters and neurotrophic factors concentration at different stages of chronic mercury intoxication (CMI). Materials and methods. A cohort examination of 69 workers (group 1) exposed to mercury, 18 individuals in the initial period of CMI (group 2), and 55 patients in the long-term period (group 3) were carried out. The content of neurotransmitters and neurotrophic factors was determined by enzyme immunoassay. The statistical processing included Wilcoxon, Kruskal-Wallis and Mann-Whitney tests. Results. Higher levels of histamine were found in group 2, low levels of metanephrine in group 1, and normetanephrine in group 3. An increase in the BDNF concentration was revealed in group 2 compared with groups 1 and 3. The content of neurotrophin-3 in group 3 was statistically significantly lower than in group 2. Conclusion. The general pattern for all stages is an increase in the norepinephrine and CNTF concentration. Mercury neurointoxication at all stages is characterized by high serotonin levels. A distinctive feature for trained workers is a compensatory increase in the normetanephrine level and a low BDNF and NT-3. For the initial period of CMI, an increase in the histamine, BDNF and NT-3 content is characteristic. The long-term period is characterized by an imbalance in the concentration of the studied neurotransmitters and neurotrophic factors.

Neurotrophic factors combined with stem cells in the treatment of sciatic nerve injury in rats:a meta-analysis

Treatment of peripheral nerve regeneration with stem cells alone has some limitations. For this reason, we evaluate the efficacy of neurotrophic factors combined with stem cell transplantation in the treatment of sciatic nerve injury in rats. PubMed, Cochrane Library, EMbase, WanFang, VIP and China National Knowledge Infrastructure databases were retrieved from inception to October 2021, and control experiments on neurotrophic factors combined with stem cells in the treatment of sciatic nerve injury in rats were searched. Nine articles and 551 rats were included in the meta-analysis. The results of meta-analysis confirmed that neurotrophic factor combined with stem cells for the treatment of sciatic nerve injury yielded more effective repair than normal rats with regard to sciatic nerve index, electrophysiological detection index, electron microscope observation index, and recovery rate of muscle wet weight. The conclusion is that neurotrophic factor combined with stem cells is more conducive to peripheral nerve regeneration and functional recovery than stem cells alone. However, due to the limitation of the quality of the included literature, the above conclusions need to be verified by randomized controlled experiments with higher quality and larger samples.

EFFECT OF GLYPROLINES ON THE LEVEL OF APOPTOTIC AND NEUROTROPHIC FACTORS UNDER CONDITIONS OF “SOCIAL” STRESS

The aim of the article was to study the effect of glyproline neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu, on the level of apoptotic factors (caspase-3, caspase-8, the tumor necrosis factor) and neurotrophic factors (the nerve growth factor and the brain neurotrophic factor) in the blood serum of white rats under the experimental modeling of “social” stress.Materials and methods. The experimental studies were carried out on 90 nonlinear white male rats aged 6 months. By the type of behavior, in the process of “social” stress modeling, all the rats were divided into “aggressors” and “victims”. In the study, the following experimental groups (n=10) were formed: control individuals; groups of the rats exposed to stress for 20 days; groups of the animals treated intraperitoneally at the dose of 100 μg/kg/day, starting from the 1st day of the stress factor exposure, with a course of 20 days of glyproline compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu. The effect of the compounds on the level of apoptotic and neurotrophic factors was assessed by determining the level of caspase-3, caspase-8, the tumor necrosis factor, the nerve growth factor and the brain neurotrophic factor of white rat blood serum by enzyme immunoassay.Results. According to the results of the study, it was found out that under the conditions of “social” stress, there was an increase in the apoptotic processes accompanied by an increase in the level of caspase-3, caspase-8, TNF-α in the blood serum of white rats, as well as a decrease in the concentration of neurotrophic factors – BDNF and NGF. The administration of giproline compounds against the background of stress, contributed to the restoration of the studied indicators level, which is most likely due to the presence of antiapoptotic and neuroprotective effects in giprolines due to the inhibition of the caspase-dependent cascade of apoptosis reactions, as well as the induction of the synthesis of neurotrophic factors with the antiapoptotic activity.Conclusion. Thus, the administration of glyproline neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu under stress conditions, contributes to the restoration of the initiating and effector caspases level, as well as of neurotrophic factors. As a result of the experiment, an anti-apoptotic effect is observed due to the inhibition of the caspase-dependent cascade of reactions, as well as a stress-protective effect is observed due to the restoration of the brain neurotrophic factors level.