Neuro faces of beneficial T cells:essential in brain,impaired in aging and neurological diseases,and activated functionally by neurotransmitters and neuropeptides

T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naive normal human T cells are:dopamine,glutamate,GnRH-Ⅱ,neuropeptide Y,calcitonin gene-related peptide,and somatostatin.Fifth, "Personalized Adoptive Neuro-Immunotherapy".This is a novel unique cellular immunotherapy,based on the "Nerve-Driven Immunity" findings,which was recently designed and patented for safe and repeated rejuvenation,activation,and improvement of impaired and dysfunctional T cells of any person in need,by ex vivo exposure of the person’s T cells to neurotransmitters and neuropeptides.Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis,and subsequent ex vivo in vivo personalized adoptive therapy,tailo red according to the diagnosis.The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans,pending validation of safety and efficacy in clinical trials,especially in brain tumors,chronic infectious diseases,and aging,in which T cells are exhausted and/or senescent and dysfunctional.

Effects of a Combination of Fu Zi and Rou Gui on Intestinal Neurotransmitters and Microflora in Rats with Slow Transit Constipation

[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae) and Rou Gui(Cortex Cinnamomi, the bark of Cinnamamunz cassia Presl of family Lauraceae) on intestinal neurotransmitters and microflora in rats with slow transit constipation(STC). [Methods] Experimental rats were given loperamide hydrochloride by gavage to induce STC, and then treated with Fu Zi alone, Rou Gui alone, a combination of Fu Zi and Rou Gui(2:1 w/w), and prucalopride, respectively, for 14 days. Meanwhile, the general condition, the time to first black stool and the rate of intestinal propulsion of rats in each group were observed after STC was induced and after drug treatment, and the pathological changes in rat colon were observed via hematoxylin-eosin(HE) staining, and the levels of colonic 5-hydroxytryptamine(HT), vasoactive intestinal peptide(VIP) and substance P(SP) were detected by ELISA, and the changes in intestinal flora were detected by 16S rRNA Real-time PCR. [Results] Compared with healthy rats, the time to first black stool and the rate of intestinal propulsion, colonic 5-HT and SP levels significantly decreased(p<0.01), while their colonic VIP level significantly increased(p<0.01). Compared with STC rats, the time to first black stool, the rate of intestinal propulsion, colonic 5-HT and SP levels in Fu Zi-Rou Gui(2:1) treated rats and prucalopride treated rats significantly increased(p<0.01), while their colonic VIP level significantly decreased(p<0.01). There was no significant difference in alpha diversity between healthy rats and STC rats. However, analysis on beta diversity revealed that there were differences in microflora structure and composition between them. Compared with healthy rats, the relative abundance of Firmicutes and Proteobacteria in STC rats significantly increased, while that of Bacteroidetes decreased. Compared with STC rats, the relative abundance of Proteobacteria decreased and that of Bacteroidetes and Firmicutes increased in Fu Zi-Rou Gui(2:1) treated rats;the relative abundance of Bacteroidetes and Proteobacteria decreased while that of Firmicutes increased in Fu Zi treated rats;the relative abundance of Proteobacteria decreased while that of Bacteroidetes increased in Rou Gui treated rats;the relative abundance of Firmicutes and Proteobacteria decreased while that of Bacteroidetes increased in prucalopride treated rats. The intestinal flora in rats of all groups was dominated by Lactobacillus spp. and other genera of anaerobic bacteria. Compared with healthy rats, the relative abundance of Lactobacillus spp. and Clostridium spp. in STC rats decreased, while those of Blautia spp. and Ruminococcus spp. and Allobaculum spp. increased. Compared with STC rats, the relative abundance of Lactobacillus spp. in all rats treated with drugs increased. [Conclusions] The combination of Fu Zi and Rou Gui(2:1) can effectively improve intestinal motility in STC rats by regulating intestinal microbial community and the levels of colonic neurotransmitters.

Effects of Subchronic Aluminum Exposure on Amino Acids Neurotransmitters in Chicken Brain

To investigate the effects of aluminium (Al) exposure on amino acid neurotransmitters, the chickens with different levels of subchronic Al poisoning were estabolished by continuous peritoneal injection of fixed volume and different concentrations of gradient of aluminium trichloride (AlCl3). The levels of amino acid neurotransmitters in chicken brains were determined by high performance liquid chromatography (HPLC) after being exposed of Al for 60 days, and Al levels in serum and brain tissue were determined by atomic absorption spectrophotometry (AAS). The results showed that Glu levels increased with the increase of Al, but there was no significant difference compared with the control. The levels of Al, Asp, Gly, GABA and Tau were significantly higher in Al-treated groups than those in the control. The results indicated that Al intoxication led to excitatory neurotoxicity.

Protective Effect of Curcumin on Anxiety, Learning Behavior, Neuromuscular Activities, Brain Neurotransmitters and Oxidative Stress Enzymes in Cadmium Intoxicated Mice

Cadmium (Cd) exposure can induce acute lethal health-related threats to humans since it has an exceptional ability to accumulate in living organisms and cause toxicological effects. Curcumin (Cur) on the other hand has a wide variety of biological activities and several animal studies have suggested for a potential therapeutic or preventive effects against several ailments and infections. To study the effect of Cur on the toxicity of Cd, sixty Swiss-Webster strain male mice were divided into 6 groups of ten each at random. Group-1 served as the na?ve control and received no treatment. Group-2, 3 and 4 were the experimental controls and were administered once a day with a single oral dose of 50% dimethyl sulphoxide (DMSO), Cur (300 mg/kg) or Cd (100 mg/kg) respectively, for 2 weeks. Group-5 and 6 received Cur and Cd in combination once a day orally for 2 weeks except that Cur in a dose of 150 and 300 mg/kg to group 5 and 6 respectively, was administered one hour before Cd (100 mg/kg) administration to both groups. After treatment period, the animals were subjected to behavioral tests and thereafter, the animals were sacrificed for the estimation of neurotransmitters like serotonin (5-HT), dopamine (DA) and it’s metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) as well as oxidative stress enzymes like lipid peroxides in the form of thiobarbituric acid–reactive substances (TBARS) and total glutathione (GSH) in the forebrain tissue. Cd reduced significantly the body weight gain, the locomotor activity, anxiety behavior in the plus maze and the learning capability (cognitive effect) in the shuttle-box test. Biochemical analysis further revealed that Cd exposure significantly altered the brain neurotransmitters and the oxidative stress enzymes. However, administration of Cur along with Cd had an ameliorating effect on all the behavioral and biochemical parameters studied herein and reduced the toxicity of Cd significantly and dose-dependently. Thus, Cur may be beneficial for anxiety, neuromuscular, and cognitive problems and protect from Cd intoxication.

Pseudotargeted metabolomics for exploring the changes of neurotransmitters profile in aging rat brain and the potential neuroprotective effect of alkaloids from Uncaria rhynchophylla

Background:Aging is an essential risk factor for most neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.However,changes in the levels of neurotransmitters that are associated with aging are not well understood.Methods:Methods such as liquid-liquid extraction,protein precipitation,and solid-phase extraction,using 20 different extraction solvents,were evaluated to optimize the extraction of neurotransmitters.A pseudotargeted metabolomics approach was developed to detect neurotransmitters in brain tissues using ultra-high-performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry.Alkaloids that crossed into the brain were used to evaluate the effect of glutamic acid-induced excitatory neurotoxicity in SH-SY5Y cells.Results:The overall extraction efficiency using protein precipitation was high.The changes in neurotransmitters’levels in the brain exhibited changes during the different growth cycles.The levels of seven neurotransmitters(aspartic acid,tyrosine,isoleucine,leucine,tryptophan,valine,andγ-aminobutyric acid)were significantly different.Meanwhile,alkaloids could reduce the excitatory neurotoxicity of glutamic acid-induced SH-SY5Y cells via suppression of oxidative stress.Conclusion:Significant differences were observed in neurotransmitter profiling between 1-and 8-month-old rats,and the discrepant neurotransmitters were associated with aging.Seven indole alkaloids from Uncaria rhynchophylla,which could cross the blood-brain barrier,were screened and used to explore their protective effects against aging.Uncaria rhynchophylla alkaloids exhibited a neuroprotective effect by inhibiting oxidative stress,indicating that the alkaloid could be a potential therapeutic candidate for neurological disorders caused by glutamic acid toxicity.

Effects of low frequency electrical stimulation on monoamine neurotransmitters,cerebral blood flow and hemorheology in children with cerebral palsy

Objective: To investigate the effects of low frequency electrical stimulation on monoamine neurotransmitters, cerebral blood flow and hemorheology in children with cerebral palsy. Methods: A total of 83 children with cerebral palsy were divided into the control group (n=42) and the observation group (n=41) according to the random data table, patients in the control group were treated with routine rehabilitation treatment, on this basis;the children in the observation group were treated with low-frequency electric stimulation. Before and after the treatment, the levels of monoamine neurotransmitter [dopamine (DA) and 5-hydroxy tryptamine (5-HT) and norepinephrine (NE)], cerebral blood flow [the average blood flow velocity of anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA)] and blood rheology index [high/low shear whole blood viscosity, plasma viscosity and fibrinogen (FIB)] of two groups were compared. Results: Before treatment, there were no significant difference of the levels of DA, 5-HT, NE, the average blood flow velocity of ACA/MCA/PCA, high/low shear whole blood viscosity, plasma viscosity and FIB between the two groups. After treatment, two groups of DA, 5-HT and NE levels were significantly higher than those in the same group before treatment, and the observation group of DA, 5-HT and NE levels were significantly higher than those of the control group, the difference was statistically significant;The average blood flow rate of ACA/MCA/PCA in the observation group after treatment was significantly higher than those in the same group before treatment;After treatment, the levels of high shear/low shear blood viscosity, plasma viscosity and FIB of the two groups were significantly lower than those in the same group before treatment, and the levels of observation group after treatment were significantly lower than that in the control group, the difference was statistically significant. Conclusion: Low frequency electrical stimulation can effectively increase the level of monoamine neurotransmitter, improve the level of cerebral blood flow and hemorheology, has an important clinical value.

Effects of Fuhe decoction on behaviors and monoamine neurotransmitters in different brain regions of CUMS combined with social isolation depression model rats

Objective:To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation(CUMS)combined with social isolation.Methods:Fifty male SD rats were randomly divided into a blank group,model group,fluoxetine group,Chaiqinwendan decoction group,and Fuhe decoction group.Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model.After 42 days of administration,a tail suspension test and high-performance liquid electrochemical detection(HPLC-ECD)were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine(NE),dopamine(DA),5-hydroxytrytamine(5-HT),and metabolites in different brain regions of rats in each group before and after treatment.Results:Compared with the model group,the epinephrine(E)content in the Fuhe decoction group was highly significantly increased(P<.01).Compared with the model group,the 5-HT content of the prefrontal cortex in rats in the Fuhe decoction group was highly significantly increased(P<.01).Furthermore,compared with the model group,the 5-HT content in the hippocampus of rats in the Fuhe decoction group was significantly increased(P<.05).Conclusion:Fuhe decoction can improve the depression-like behaviors of model rats,and its antidepressant effect may be related to the increase in 5-HT content in the prefrontal cortex and hippocampus of rats.

Effect of zopiclone combined with Deanxit on cytokines and neurotransmitters in patients with poststroke depression

Objective: To explore the effect of zopiclone combined with Deanxit on cytokines and neurotransmitters in patients with poststroke depression. Methods: A total of 78 patients with poststroke depression who were treated in Zaozhuang Mining Group Dongjiao Hospital between January 2015 and February 2017 were divided into control group (n=41, receiving conventional Deanxit therapy) and zopiclone group (n=37, receiving zopiclone combined with Deanxit therapy). The differences in serum nerve injury marker, inflammatory cytokine and monoamine neurotransmitter levels were compared between the two groups before treatment and after 12 weeks of treatment. Results: Before treatment, serum levels of nerve injury markers, inflammatory cytokines and monoamine neurotransmitters were not significantly different between the two groups. After 12 weeks of treatment, serum nerve injury markers NSE and S100B levels of zopiclone group were lower than those of control group whereas BDNF level was higher than that of control group;serum inflammatory cytokines IL-1, IL-2, IL-23 and TNF-α levels of zopiclone group were lower than those of control group;serum monoamine neurotransmitters NE, 5-HT and DA levels of zopiclone group were higher than those of control group. Conclusion: Zopiclone combined with Deanxit therapy can effectively optimize the neurological function, reduce the inflammatory response and increase the secretion of monoamine neurotransmitters in patients with poststroke depression.

Relationship of serum neurotransmitters with anxiety depression, T lymphocyte subsets and NK cells in patients with lung cancer chemotherapy

Objective:To study the relationship of serum neurotransmitters with anxiety depression, T lymphocyte subsets and NK cells in patients with lung cancer chemotherapy.Methods: 56 cases of patients with advanced lung cancer who received chemotherapy in the First Affiliated Hospital of Chengdu Medical College between July 2013 and August 2016 were collected as observation group, and 50 healthy subjects who received physical examination in our hospital during the same period were selected as normal control group. Serum neurotransmitter, negative emotions and immune index levels were compared between the two groups of subjects. Pearson test was used to evaluate the relationship of serum neurotransmitter contents with negative emotions and immune index levels in patients with lung cancer chemotherapy. Results: Serum neurotransmitters DA, 5-HT and NE contents in observation group were lower than those in normal control group;SAS and SDS scores were higher than those of normal control group;peripheral blood CD4+T lymphocyte level, CD4+/CD8+ ratio and NK cell level were lower than those in normal control group while CD8+ T lymphocyte level was higher than that in normal control group. Pearson test showed that serum neurotransmitters DA, 5-HT and NE contents in patients with lung cancer chemotherapy were directly correlated with anxiety depression, T lymphocyte subset and NK cell levels.Conclusion: Serum neurotransmitter expression decrease in patients with lung cancer chemotherapy, and this is one of the important causes of anxiety depression and immune dysfunction in patients.

Effects of dexzopiclone and estazolam on neurotransmitters, nerve cytokines and stress states in patients with insomnia after stroke

Objective:To study the effects of dexzopiclone and estazolam on neurotransmitters, nerve cytokines and stress states in patients with insomnia after stroke.Methods: The patients with insomnia after stroke who were treated in Linyi Rongjun Hospital between March 2015 and October 2017 were chosen and randomly divided into dexzopiclone group and estazolam group. The levels of neurotransmitters, nerve cytokines and stress indexes in serum were measured before treatment as well as 14 days and 28 days after treatment.Results: Compared with those before treatment, serum Glu,γ-GABA, 5-HT, 5-HIAA, BDNF and NGF levels of both groups significantly increased whereas NE, TNF-α, IL-6, ATCH, Cor, CRP, SOD and GSH levels significantly decreased after treatment, and serum Glu,γ-GABA, 5-HT, 5-HIAA, BDNF and NGF levels of dexzopiclone group after treatment were higher than those of estazolam group whereas NE, TNF-α, IL-6, ATCH, Cor, CRP, SOD and GSH levels were lower than those of estazolam group.Conclusion:Dexzopiclone is more effective than estazolam to regulate the secretion of neurotransmitters and nerve cytokines and reduce the stress state in patients with insomnia after stroke.

Effect of diazocine combined with sufentanil analgesia after radical operation for esophageal cancer on the release of neurotransmitters and stress mediators

Objective:To study the effect of diazocine combined with sufentanil analgesia after radical operation for esophageal cancer on release of neurotransmitters and stress mediators.Methods:A total of 170 cases of patients with primary esophageal cancer who underwent surgical treatment in this hospital between September 2015 and May 2017 were divided into control group (n=85) and study group (n=85) by random number table method. Control group received postoperative sufentanil analgesia, and study group received postoperative diazocine combined with sufentanil analgesia. The differences in the perioperative contents of monoamine neurotransmitters, amino acid neurotransmitters and stress mediators were compared between the two groups.Results: Before operation, there was no statistically significant difference in the serum contents of monoamine neurotransmitters, amino acid neurotransmitters and stress mediators between the two groups. 12 h after surgery, 24 h after surgery and 36 h after surgery, serum monoamine neurotransmitters DA, NE and 5-HT contents of study group were lower than those of control group;amino acid neurotransmitters Ach, GABA and Glu contents were higher than those of control group;serum stress mediators ACTH, ALD and Cor contents were lower than those of control group.Conclusion: diazocine combined with sufentanil analgesia after radical operation for esophageal cancer can effectively optimize the secretion of neurotransmitters and inhibit the synthesis of stress mediators to alleviate the patients' pain perception.

Effects of routine rehabilitation therapy combined with low frequency electrical stimulation on monoamine neurotransmitters, NSE, ET-1 and cerebral hemodynamics in children with cerebral palsy

Objective:To investigate the effects of routine rehabilitation therapy combined with low frequency head stimulation on monoamine neurotransmitters, neuron-specific enolase (NSE), endothelin-1 (ET-1) and cerebral hemodynamics in children with cerebral palsy.Methods:From January 2017 to June 2018, 110 children with cerebral palsy were randomly divided into observation group (55 cases) and control group (55 cases). The control group received routine rehabilitation treatment, while the observation group received low-frequency head stimulation on the basis of routine rehabilitation treatment. The changes of dopamine (DA), norepinephrine (NE), serotonin (5-HT), NSE, ET-1 levels and mean blood flow velocity of anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) were compared in two groups.Results:Before treatment, there was no significant difference in DA, NE and 5-HT levels in two groups. After treatment, DA, NE and 5-HT levels in the observation group were (192.23±22.71) ng/mL, (98.02±11.71) ng/L, (210.07±25.03) ng/L, and in the control group. the DA, NE, 5-HT levels were (147.06±17.02) ng/mL, (83.07±11.15) ng/L, and (171.88±20.45) ng/L, respectively. The DA, NE and 5-HT levels in two groups were higher than those before treatment, and DA, NE and 5-HT levels in the observation group were higher than those in the control group. Before treatment, there was no significant difference in NSE and ET-1 levels between the two groups. After treatment, the NSE and ET-1 levels in the observation group were (7.97±2.07) μg/L and (41.01±10.07) pg/mL, and the NSE and ET-1 levels in the control group were (10.38±3.02) μg/L, (58.46±15.02) pg/mL, respectively. the NSE and ET-1 in two groups were lower than those before treatment, and the NSE and ET-1 of the observation group were lower than the control group. Before treatment, there was no significant difference in mean blood flow velocity between ACA, MCA and PCA. After treatment, the mean blood flow velocities of ACA, MCA, and PCA in the observation group were (46.88±7.72) cm/s, (59.85±10.18) cm/s, and (49.15±7.02) cm/s, respectively, which was significantly higher than before treatment and higher than that of the control group in the same period.Conclusion: Conventional rehabilitation combined with low-frequency electrical stimulation of the head can effectively increase the content of monoamine neurotransmitters in children with cerebral palsy, enhance cerebral blood circulation, and reduce brain damage.

Effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy

Objective:To study the effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy.Methods:Patients with advanced cervical cancer who received chemotherapy in the First Affiliated Hospital of Chengdu Medical College between May 2014 and June 2016 were selected, HAMA scores and HAMD scores were used to assess anxiety and depression and divide the patients into control group, depression group, anxiety group and depression + anxiety group. The contents of monoamine neurotransmitters and immune cytokines in serum as well as the expression of immune transcription factors in peripheral blood mononuclear cells were detected.Results:Serum NE, E, 5-HT, 5-HIAA and DOPAC contents of depression group and depression + anxiety group were significantly lower than those of control group, and serum NE, E, 5-HT, 5-HIAA and DOPAC contents of anxiety group were significantly higher than those of control group;peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression group, anxiety group and depression + anxiety group were significantly lower than those of control group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of control group;peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression + anxiety group were significantly lower than those of depression group and anxiety group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of depression group and anxiety group. Conclusion: Anxiety and depression in patients with cervical cancer chemotherapy can affect the secretion of monoamine neurotransmitters, the differentiation of CD4+T cell subsets and the antitumor immune response mediated by them.

Effect of dialectical behavior therapy on the serum neurotransmitters and cytokines in depression patients with suicidal tendency

Objective: To explore the effect of dialectical behavior therapy on the serum neurotransmitters and cytokines in depression patients with suicidal tendency. Methods: A total of 98 depression patients with suicidal tendency who were treated in the hospital between August 2014 and August 2017 were collected and divided into the control group (n=49) and the research group (n=49) by random number table. Control group received routine drug therapy, and study group received dialectical behavior therapy combined with drug therapy. The differences in serum levels of monoamine neurotransmitters, nerve function indexes and acute phase proteins were compared between the two groups of patients. Results: After treatment, serum NE, 5-HT and DA levels of research group were higher than those of control group;serum MBP and NSE levels of research group were lower than those of control group while BDNF level was higher than that of control group;serum Tf level of research group was higher than that of control group while Hp level was lower than that of control group. Conclusion: Dialectical behavior therapy intervention can effectively optimize the nerve function and improve the overall state of depression patients with suicidal tendency.

Effect of ropivacaine combined with sufentanil epidural labor analgesia on pain neurotransmitters as well as cytokine production and stress hormone secretion

Objective: To discuss the effect of ropivacaine combined with sufentanil epidural labor analgesia on pain neurotransmitters as well as cytokine production and stress hormone secretion. Methods: A total of 218 cases of puerperae who received caesarean section in the hospital between January 2015 and January 2017 were divided into control group (n=109) and observation group (n=109) by random table method. Control group received postpartum ropivacaine epidural analgesia alone, and observation group received postpartum ropivacaine combined with sufentanil epidural analgesia. The differences in serum levels of pain neurotransmitters, inflammatory factors and stress hormones were compared between the two groups immediately after childbirth (T0), 6 h after delivery (T1), 12 h after delivery (T2) and 24 h after delivery (T3). Results: At T0, the differences in serum levels of pain neurotransmitters, inflammatory factors and stress hormones were not statistically significant between the two groups. At T1, T2 and T3, serum NPY, β-EP and SP levels of observation group were lower than those of control group at corresponding points in time;serum IL-1β, hs-CRP and IL-6 levels of observation group were lower than those of control group at corresponding points in time;serum Cor, AngⅠ, AngⅡ and NE levels of observation group were lower than those of control group at corresponding points in time. Conclusion:Ropivacaine combined with sufentanil epidural analgesia after caesarean section can effectively inhibit the pain neurotransmitter expression and relieve the systemic inflammatory stress response in puerperae.

Effect of mild hypothermia intervention on the nerve injury as well as neurotransmitters and inflammatory mediators in patients with acute craniocerebral injury

Objective: To explore the effect of mild hypothermia intervention on the nerve injury as well as neurotransmitters and inflammatory mediators in patients with acute craniocerebral injury. Methods: A total of 700 patients with acute craniocerebral injury who were treated in Lueyang People's Hospital between March 2014 and March 2017 were collected and divided into routine group (n=350) and mild hypothermia group (n=350) by random number table. Routine group accepted craniotomy evacuation of hematoma, and mild hypothermia group accepted mild hypothermia intervention on the basis of craniotomy evacuation of hematoma. The differences in the serum contents of nerve injury-related indexes, amino acid neurotransmitters and inflammatory mediators were compared between the two groups before and after treatment. Results: Before treatment, there was no statistically significant difference in the serum levels of nerve injury-related indexes, amino acid neurotransmitters and inflammatory mediators between the two groups. After treatment, serum nerve injury-related indexes NSE, S100B, Nogo-A and MBP levels of mild hypothermia group were lower than those of routine group;serum amino acid neurotransmitters Asp and Glu levels of mild hypothermia group were lower than those of routine group while GABA level was higher than that of routine group;serum inflammatory mediators HMGB1, IL-8 and TNF-α levels of mild hypothermia group were lower than those of routine group. Conclusion: Early mild hypothermia intervention can effectively relieve the nerve injury in patients with acute craniocerebral injury and exert positive neuroprotective effect.

Effect of adjuvant acupuncture therapy on serum cytokines and neurotransmitters in patients with post-stroke depression

Objective:To study the effect of adjuvant acupuncture therapy on serum cytokines and neurotransmitters in patients with post-stroke depression.Methods: Patients with poststroke depression who were treated in Traditional Chinese Medicine Hospital of Yuyang District Yulin City between May 2014 and February 2017 were selected as the research subjects and divided into two groups by random number table, control group of patients received neurotrophy, rehabilitation exercise, antidepressant drugs and other symptomatic treatment, and the acupuncture group received auxiliary acupuncture treatment on the basis of symptomatic treatment. The serum levels of nerve cytokines, inflammatory cytokines and neurotransmitters were detected before treatment as well as 2 weeks and 4 weeks after treatment.Results: 2 weeks and 4 weeks after treatment, serum BDNF, NGF, IGF-1, FGF-2, NE, DA and 5-HT levels of both groups of patients were higher than those before treatment while HCY, IL-1β, IL-2, sIL-2R, TNF-α levels were lower than those before treatment, and serum BDNF, NGF, IGF-1, FGF-2, NE, DA and 5-HT levels of acupuncture group were higher than those of control group while HCY, IL-1β, IL-2, sIL-2R, TNF-α levels were lower than those of control group.Conclusion: Adjuvant acupuncture therapy for post-stroke depression can increase the secretion of nerve cytokines, reduce the secretion of inflammatory cytokines and regulate the function of monoamine neurotransmitters.

Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes

BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive dysfunction.Hyperglycemia is closely related to neurological abnormalities,while often disregarded in clinical practice.Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)levels.METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital.The participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical indicators.Meanwhile,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.RESULTS The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-1.188,P<0.01)were independent predictors of poor glycemic control.CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control,which may be the basis for the changes in cognitive function in diabetic patients.

Analysis of neurotransmitters validates the importance of the dopaminergic system in autism spectrum disorder

Background The reasons behind the cardinal symptoms of communication deficits and repetitive,stereotyped behaviors that characterize autism spectrum disorder(ASD)remain unknown.The dopamine(DA)system,which regulates motor activity,goal-directed behaviors,and reward function,is believed to play a crucial role in ASD,although the exact mechanism is still unclear.Investigations have shown an association of the dopamine receptor D4(DRD4)with various neurobehavioral disorders.Methods We analyzed the association between ASD and four DRD4 genetic polymorphisms,5′flanking 120-bp duplication(rs4646984),rs1800955 in the promoter,exon 112 bp duplication(rs4646983),and exon 348 bp repeats.We also examined plasma DA and its metabolite levels,DRD4 mRNA expression,and correlations of the studied polymorphisms with these parameters by case–control comparative analyses.The expression of DA transporter(DAT),which is important in regulating the circulating DA level,was also evaluated.Results A significantly higher occurrence of rs1800955“T/TT”was observed in the probands.ASD traits were affected by rs1800955“T”and the higher repeat alleles of the exon 348 bp repeats,rs4646983 and rs4646984.ASD probands exhibited lower DA and norepinephrine levels together with higher homovanillic acid levels than the control subjects.DAT and DRD4 mRNA expression were down-regulated in the probands,especially in the presence of DAT rs3836790“6R”and rs27072“CC”and DRD4 rs4646984 higher repeat allele and rs1800955“T”.Conclusion This pioneering investigation revealed a positive correlation between genetic variants,hypodopaminergic state,and impairment in socio-emotional and communication reciprocity in Indian subjects with ASD,warranting further in-depth analysis.