scholarly journals The Parasympathetic Nervous System in the Quest for Stroke Therapeutics

2011 ◽  
Vol 31 (5) ◽  
pp. 1187-1195 ◽  
Author(s):  
Cletus Cheyuo ◽  
Asha Jacob ◽  
Rongqian Wu ◽  
Mian Zhou ◽  
Gene F Coppa ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Parasympathetic Nervous System ◽  
Brain Disorders ◽  
Stroke Therapy ◽  
Successful Development ◽  
Oxidative And Nitrosative Stress ◽  
Anatomical Basis ◽  
Further Development

Stroke is a devastating neurovascular disease with limited therapeutic options. The pathogenesis of stroke involves complex interrelated molecular mechanisms including excitotoxicity, oxidative and nitrosative stress, cortical spreading depolarizations, inflammation, necrosis, and apoptosis. Successful development of stroke therapeutics depends on understanding these molecular mechanisms and how to counteract them to limit tissue damage during stroke. Activation of the parasympathetic nervous system (PNS) has been shown to antagonize a multiplicity of pathologic mechanisms. Elements of parasympathetic activation such as vagus nerve stimulation have already been used successfully in treating brain disorders such as epilepsy and depression. This review discusses the anatomical basis and molecular mechanisms involved in activation of the PNS, and assesses the strength of available evidence for the further development of this modality into a stroke therapy.

scholarly journals The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 121 ◽  
Author(s):  
Yonghee Kim ◽  
Jinhong Park ◽  
Yoon Kyung Choi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Bk Channel ◽  
Cns Injury ◽  
Antioxidant Agents ◽  
The Central Nervous System

Astrocytes outnumber neurons in the human brain, and they play a key role in numerous functions within the central nervous system (CNS), including glutamate, ion (i.e., Ca2+, K+) and water homeostasis, defense against oxidative/nitrosative stress, energy storage, mitochondria biogenesis, scar formation, tissue repair via angiogenesis and neurogenesis, and synapse modulation. After CNS injury, astrocytes communicate with surrounding neuronal and vascular systems, leading to the clearance of disease-specific protein aggregates, such as β-amyloid, and α-synuclein. The astrocytic big conductance K+ (BK) channel plays a role in these processes. Recently, potential therapeutic agents that target astrocytes have been tested for their potential to repair the brain. In this review, we discuss the role of the BK channel and antioxidant agents such as heme oxygenase metabolites following CNS injury. A better understanding of the cellular and molecular mechanisms of astrocytes’ functions in the healthy and diseased brains will greatly contribute to the development of therapeutic approaches following CNS injury, such as Alzheimer’s disease, Parkinson’s disease, and stroke.

Altered plasma proteome during an early phase of peritonitis-induced sepsis

2009 ◽  
Vol 116 (9) ◽  
pp. 721-730 ◽  
Author(s):  
Visith Thongboonkerd ◽  
Wararat Chiangjong ◽  
Jan Mares ◽  
Jiri Moravec ◽  
Zdenek Tuma ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Inflammatory Responses ◽  
Sepsis Syndrome ◽  
Host Responses ◽  
Plasma Proteome ◽  
Oxidative And Nitrosative Stress ◽  
Two Dimensional Gel Electrophoresis ◽  
Human Sepsis ◽  
Altered Proteins

Sepsis is a systemic response to infection commonly found in critically ill patients and is associated with multi-organ failure and high mortality rate. Its pathophysiology and molecular mechanisms are complicated and remain poorly understood. In the present study, we performed a proteomics investigation to characterize early host responses to sepsis as determined by an altered plasma proteome in a porcine model of peritonitis-induced sepsis, which simulated several clinical characteristics of human sepsis syndrome. Haemodynamics, oxygen exchange, inflammatory responses, oxidative and nitrosative stress, and other laboratory parameters were closely monitored. Plasma samples were obtained from seven pigs before and 12 h after the induction of sepsis, and plasma proteins were resolved with two-dimensional gel electrophoresis (n=7 gels/group; before being compared with during sepsis). The resolved proteins were stained with the SYPRO Ruby fluorescence dye and subjected to quantitative and comparative analyses. From approx. 1500 protein spots visualized in each gel, levels of 36 protein spots were significantly altered in the plasma of animals with sepsis (sepsis/basal ratios or degrees of change ranged from 0.07 to 21.24). Q-TOF (quadrupole–time-of-flight) MS and MS/MS (tandem MS) identified 30 protein forms representing 22 unique proteins whose plasma levels were increased, whereas six forms of five unique proteins were significantly decreased during sepsis. The proteomic results could be related to the clinical features of this animal model, as most of these altered proteins have important roles in inflammatory responses and some of them play roles in oxidative and nitrosative stress. In conclusion, these findings may lead to a better understanding of the pathophysiology and molecular mechanisms underlying the sepsis syndrome.

scholarly journals Antidepressant Like Effect of Sodium Orthovanadate in A Mouse Model of Chronic Unpredictable Mild Stress.

2021 ◽  
Author(s):  
Angel Joshi ◽  
Ansab Akhtar ◽  
Priyanka Saroj ◽  
Anurag Kuhad ◽  
Sangeeta Pilkhwal Sah
Keyword(s):  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Tyrosine Phosphatase ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sodium Orthovanadate ◽  
Behavioral Tests ◽  
Oxidative And Nitrosative Stress

Abstract Depression is a psychiatric disorder characterized by low esteem, anhedonia, social deficit, and lack of interest. Decreased BDNF and impaired TrKB signaling be associated with depression. In our study, depressive-like behavior was induced in mice by chronic unpredictable mild stress (CUMS) model. Various behavioral tests like tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT); biochemical analyses for corticosterone, reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), nitric oxide (NO) and ELISA for BDNF were performed. Body weight was measured every week. Depressive-like behavior was associated with increased oxidative stress in the brain and subsequent reduction of BDNF. Further, sodium orthovanadate (SOV), a protein tyrosine phosphatase inhibitor was used as a test drug as it is reported to stimulate BDNF levels. Sodium orthovanadate (SOV-5 mg/kg, 10 mg/kg) and fluoxetine (10 mg/kg) was given to mice orally for 21 days before 30 minutes of stress induction. The behavioral tests reflected depressive-like behavior in CUMS, which was attenuated by both SOV and fluoxetine. SOV at 10 mg/kg has demonstrated significant results in our study by decreasing malondialdehyde levels (MDA/LPO), NO levels, and increasing GSH and SOD in both the cortex and hippocampus. Besides, ELISA revealed the elevation of BDNF levels in the treatment groups (SOV-5 mg/kg, 10 mg/kg, and FLX-10 mg/kg) as compared with the disease group (CUMS). Therefore, the treatment with SOV appeared to reverse both oxidative and nitrosative stress. Decreased serum corticosterone levels (SOV-5 mg/kg, 10 mg/kg); FLX (10 mg/kg) + SOV (5 mg/kg); FLX-10 mg/kg and per-se) and elevated BDNF level (SOV-5 mg/kg, 10 mg/kg and FLX-10 mg/kg) were associated with attenuation of depressive-like behavior. The findings of this preliminary study indicate that SOV has the potential to restore antidepressant-like effect or prevention of stress-induced anhedonia and so further molecular mechanisms will be warranted for clinical translation.

scholarly journals DIABETIC NEUROPATHY: MOLECULAR MECHANISMS OF DEVELOPMENT AND POSSIBILITIES FOR PATHOGENETIC THERAPY

2019 ◽  
pp. 8-12
Author(s):  
N.V. Hudiakova ◽  
N.V. Ivanov ◽  
I. Yu. Pchelin ◽  
A.N. Shishkin ◽  
N.V. Vorokhobina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Neuropathy ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Treatment Options ◽  
Neurological Complications ◽  
Diabetic Patients ◽  
Oxidative And Nitrosative Stress ◽  
Pathogenetic Therapy ◽  
Mechanisms Of Development

The present review summarizes the results of global studies and assesses contribution of hyperglycemia towards formation of neurologic complications in diabetic patients. Hyperglycemia is believed to play a leading role in the formation of neurological complications in diabetes mellitus. However, the achievement of normalization of glycemia level does not ensure the cessation of their development and progression, which indicates a lack of knowledge about the pathogenetic relationships in diabetic neuropathy. Limited understanding of these issues entails the absence of treatment options that effectively affect the course of this complication. Based on the analysis of experimental and clinical studies of recent years, data on the molecular-biological relationships of hyperglycemia with the formation of neurological complications in diabetes mellitus are summarized. The influence of the oxidative and nitrosative stress, advanced glycation end products, the activation of the polyol and hexosamine pathways on the state of the nerve fiber is analyzed. The data on molecular mechanisms of development of diabetic neuropathy are contradictory. On the basis of recent experimental and clinical data we review possibilities for pathogenetic therapy. The problem of oppositely directed effects of treatment is discussed. Clinical rationale is given for declared direction of further studies.

scholarly journals Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures

2015 ◽  
Vol 18 (4) ◽  
pp. 661 ◽  
Author(s):  
John Richard Bend ◽  
Xue Yan (Iris) Xue Yan Xia ◽  
Daofeng Chen ◽  
Abudi Awaysheh ◽  
Andrea Lo ◽  
...  
Keyword(s):  
Real Time ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Fluorescent Protein ◽  
Antioxidant Properties ◽  
Oxidative And Nitrosative Stress ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells

PURPOSE:  Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer’s. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells. METHODS: Endpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status. RESULTS: At low µM concentrations, each of the TCM constituents and mixtures effectively attenuated intracellular toxicity due to exposure of HEK 293 cells to 50 or 250 µM tBHP for 30 min to 3 h. Confocal microscopy of HEK 293 cells transfected with mutated green fluorescent protein (roGFP2) showed effective attenuation of tBHP oxidation by baicalein in real time. Three redox-regulated proteins prominent in the disulfide proteome of HEK 293 cells were identified by MALDI-TOF mass spectrometry. CONCLUSIONS: We conclude that single TCM chemicals and their simple mixtures have potential for use in adjunct chemoprotective therapy. Advantages of mixtures compared to single TCM constituents include the ability to combine compounds with varying molecular mechanisms of cytoprotection for enhanced biological activity; and to combine chemicals with complementary pharmacokinetic properties to increase half-life and prolong activity in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals A Putative P-Type ATPase, Apt1, Is Involved in Stress Tolerance and Virulence in Cryptococcus neoformans

2009 ◽  
Vol 9 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Guanggan Hu ◽  
James W. Kronstad
Keyword(s):  
Membrane Fusion ◽  
Cryptococcus Neoformans ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Brefeldin A ◽  
Antifungal Drugs ◽  
Oxidative And Nitrosative Stress ◽  
Transport Pathways ◽  
P Type

ABSTRACT The export of virulence factors, such as the capsule polysaccharide, to the cell surface is a critical aspect of the pathogenicity of Cryptococcus neoformans. A view of capsule export via exocytosis and extracellular vesicles is emerging, but the molecular mechanisms underlying virulence factor transport pathways remain to be established. In this study, we characterized the APT1 gene, which encodes a predicted integral membrane P-type ATPase belonging to the type IV, Drs2 family of aminophospholipid translocases (flippases) (APTs). APTs maintain the phospholipid asymmetry that is critical in membrane fusion events for trafficking and in establishing cell polarity. Deletion of the APT1 gene resulted in phenotypes consistent with similar roles in C. neoformans. These included altered actin distribution, increased sensitivity to stress conditions (oxidative and nitrosative stress) and to trafficking inhibitors, such as brefeldin A and monensin, a reduction in exported acid phosphatase activity, and hypersensitivity to the antifungal drugs amphotericin B, fluconazole, and cinnamycin. However, there was no difference in growth, capsule size, or melanin production between the wild type and the apt1 mutant strains at either 30°C or 37°C. Despite the absence of an influence on these major virulence factors, Apt1 was required for survival during interactions with macrophages, and apt1 mutants exhibited attenuated virulence in a mouse inhalation model of cryptococcosis. Therefore, Apt1 contributes to virulence and the stress response in C. neoformans through apparent functions in membrane fusion and trafficking that do not influence the deposition of major virulence factors, such as capsule and melanin, outside the cell.

scholarly journals Electroacupuncture brain protection during ischemic stroke: A role for the parasympathetic nervous system

2017 ◽  
Vol 38 (3) ◽  
pp. 479-491 ◽  
Author(s):  
Laiting Chi ◽  
Kairong Du ◽  
Dongdong Liu ◽  
Yulong Bo ◽  
Wenzhi Li
Keyword(s):  
Nervous System ◽  
Parasympathetic Nervous System ◽  
Infarct Volume ◽  
Mrna Level ◽  
Experimental Stroke ◽  
Motor Nucleus ◽  
Stroke Therapy ◽  
Dorsal Motor Nucleus ◽  
Alternative Modality ◽  
Parasympathetic Dysfunction

The demand for using parasympathetic activation for stroke therapy is unmet. In the current study, we investigated whether the neuroprotection provided by electroacupuncture (EA) in an experimental stroke model was associated with activation of the parasympathetic nervous system (PNS). The results showed that parasympathetic dysfunction (PD), performed as unilateral vagotomy combined with peripheral atropine, attenuated both the functional benefits of EA and its effects in improving cerebral perfusion, reducing infarct volume, and hindering apoptosis, neuronal and peripheral inflammation, and oxidative stress. Most importantly, EA rats showed a dramatically less reduction in the mRNA level of choline acetyltransferase, five subtypes of muscarinic receptors and α7nAChR, suggesting the inhibition of the impairment of the central cholinergic system; EA also activated dorsal motor nucleus of the vagus, the largest source of parasympathetic pre-ganglionic neurons in the lower brainstem (detected by c-fos immunohistochemistry), and PD suppressed these changes. These findings indicated EA may serve as an alternative modality of PNS activation for stroke therapy.

scholarly journals Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110576
Author(s):  
Hayder M. Al-kuraishy ◽  
Ali I. Al-Gareeb ◽  
Safaa Qusti ◽  
Eida M. Alshammari ◽  
Gideon Ampoma. Gyebi ◽  
...  
Keyword(s):  
Nervous System ◽  
Parasympathetic Nervous System ◽  
Renin Angiotensin System ◽  
Hormonal Stimulation ◽  
Angiotensin System ◽  
Autonomic Pathway ◽  
Sympathetic Storm ◽  
Further Development ◽  
Post Infectious ◽  
Pro Inflammatory Cytokines

Among the plethora of debilitating neurological disorders of COVID-19 syndrome in survivors, the scope of SARS-CoV-2-induced dysautonomia (DNS) is yet to be understood, though the implications are enormous. Herein, we present an inclusive mini-review of SARS-CoV-2-induced DNS and its associated complications. Although, the direct link between Covid-19 and DSN is still speculative, the hypothetical links are thought to be either a direct neuronal injury of the autonomic pathway or a para/post-infectious immune-induced mechanism. SARS-CoV-2 infection-induced stress may activate the sympathetic nervous system (SNS) leading to neuro-hormonal stimulation and activation of pro-inflammatory cytokines with further development of sympathetic storm. Sympathetic over-activation in Covid-19 is correlated with increase in capillary pulmonary leakage, alveolar damage, and development of acute respiratory distress syndrome. Furthermore, SARS-CoV-2 can spread through pulmonary mechanoreceptors and chemoreceptors to medullary respiratory center in a retrograde manner resulting in sudden respiratory failure. Taken together, DSN in Covid-19 is developed due to sympathetic storm and inhibition of Parasympathetic nervous system-mediated anti-inflammatory effect with development of cytokine storm. Therefore, sympathetic and cytokine storms together with activation of Renin-Angiotensin-System are the chief final pathway involved in the development of DSN in Covid-19.

scholarly journals NEUROIMMUNOENDOCRINE REGULATION OF THE SKIN FUNCTIONING

2019 ◽  
Vol 21 (5) ◽  
pp. 807-820
Author(s):  
O. A. Bashkina ◽  
M. A. Samotrueva ◽  
A. K. Azhikova ◽  
L. R. Paknnova
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Parasympathetic Nervous System ◽  
Skin Diseases ◽  
Healing Process ◽  
Skin Inflammation ◽  
Skin Wound ◽  
Social Consequences ◽  
Immune Functions ◽  
Bioactive Substances

The review deals with modern ideas of neuroimmunoendocrine regulation of physiological and pathophysiological processes in skin. The present data are provided which indicate to composite mechanisms of intercellular interactions in complex regulating systems (nervous, immune, endocrine) acting at the level of skin in normal conditions, as well during the posttraumatic period. We describe different modes for participation of endocrine and nervous systems in immunologically induced skin inflammation. The data are provided confirming localization of adrenergic receptors on membranes of immunocompetent cells and leukocytes, on regulatory effects of hypothalamus upon immune functions, about multidirectional actions upon inflammation of sympathetic and parasympathetic nervous system etc.There are sufficient data on promotion of pathophysiological changes and reconstitution processes in the skin due to effects of local immune cells and bioactive substances expressed by them. The course of skin wound regeneration depend on the type of damage, degree and a phase of healing process. Posttraumatic reparative potential of skin is often limited by the infectious processes initiated by local microflora, products of cell disintegration and necrotic tissues. The cause-effect relationship is proven by arising inflammation which is implemented by inclusion of immune protection responses. The increased necrotic area and suppuration of the wound occurs die to inhibition of system of the phagocytizing macrophages. However, activation of this system brings about formation of the connective tissue capsule around the inflammation focus within early terms.We also discuss the issues of reparative skin regeneration which of great medico-social value, in connection with considerable prevalence of traumatic events and their social consequences, followed by expressed cosmetic defects. Evolving neurocognitive problems lead to decreased quality of the patient’s life, development of social disadaptation and further deprivation. The role of nervous system and psychological frustration in genesis of skin manifestations requires future development of the modern scientific direction, i.e., psychodermatology.Understanding of molecular mechanisms regulating the neuroimmunocutaneous interactions offers new prospectives in treatment of some skin diseases, as well as activation of the damaged skin recovery. According to the data presented in the review article, one may conclude on relevance of further studies on reparative potential of skin under interactions of homeostatic regulatory systems.

Abstract 285: Reduced Parasympathetic Activity and Correlation with Plasma Resistin Levels in High Fat Diet Mice

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Sigurd Hartnett ◽  
Yifan Li
Keyword(s):  
Heart Rate ◽  
Nervous System ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Parasympathetic Nervous System ◽  
Parasympathetic Activity ◽  
Strong Positive Correlation ◽  
Mice Model ◽  
High Fat ◽  
Parasympathetic System

A trait of most cardiovascular diseases, obesity, and aging is autonomic imbalance with increased sympathetic and decreased parasympathetic activity. While the hyperactive sympathetic nervous system has been extensively researched, little attention has been given to the mechanisms involved in the reduction of the parasympathetic nervous system. This study investigates the peripheral regulation of the parasympathetic nervous system and its association with plasma resistin levels in a high fat diet mice model of obesity. Male ICR mice were fed a high fat diet (HFD) or low fat diet (LFD) for 14 weeks. At the end of the diet regimen, mice underwent vagal stimulation (VS) tests and were sacrificed for blood and tissue collection. For VS, under anesthesia of intraperitoneal injection with urethane (2 g/kg), the right cervical vagus nerve was stimulated at 2 to 10Hz with pulses of 2ms and 2V while the heart rate was monitored with ECG. The reduction of heart rate by VS was significantly attenuated at 10Hz in HFD mice as compared to LFD mice (-121.3 beats per minute, 95% Confidence Interval [CI] -178 to -64.63, p<0.05, n=5 both groups). To evaluate the contribution of adipokines and cytokines to this reduced parasympathetic response, serum was tested using commercially available kits for resistin, adiponectin, TNFa, and IL6. Whereas no changes were observed in plasma adiponectin, TNFa, or IL6 levels, there was an significant increase in plasma resistin levels in HFD mice as compared to LFD mice (837 pg/mL, 95% CI 294-1379, p<0.01, LFD n=5, HFD n=4). Furthermore, a Pearson product-moment correlation coefficient was calculated to assess the relationship between plasma resistin level and responses in heart rate to VS. There was a strong positive correlation between these two variables (r=0.851, n=8, p<0.01). The molecular mechanisms responsible for the effects of resistin on the cholinergic, parasympathetic system are currently being investigated. In summary, these results suggest that elevated plasma resistin levels may contribute to a reduction in parasympathetic nervous system activity associated with obesity.

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