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1.
目的 银椴苷(Tiliroside,Tle)是一种天然产物,存在于结香花(Edgeworthia chrysantha Lindl.)、金英(Galphimia gracilis)、和Phlomoides spectabilis等生物体中。本文主要探讨Tle对脂多糖(lipopolysaccharide,LPS)激活的原代小胶质细胞的M1/M2极化的转化作用及其抑制神经炎症反应的影响。方法 MTT检测各浓度Tle对LPS激活的原代小胶质细胞活性的影响;Griess试剂检测LPS激活的原代小胶质细胞的一氧化氮(Nitric oxide,NO)产物生成量的影响;ELISA法检测Tle对LPS激活的原代小胶质细胞的肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)蛋白水平的影响;qRT-PCR检测Tle对LPS激活的原代小胶质细胞的精氨酸酶-1(Arginase-1,Arg-1)和胰岛素生长因子-1(Insulin growth factor-1,IGF-1)的mRNA表达水平。结果 Tle(0-80 μmol·L-1)对LPS激活的原代小胶质细胞活性没有明显影响;Tle显著降低LPS激活的原代小胶质细胞亚硝酸盐的含量,并对炎症因子IL-6、TNF-α蛋白水平有显著抑制作用,同时显著提高抗炎因子Arg-1和IGF-1的mRNA水平。结论 Tle能够通过促进LPS激活的原代小胶质细胞M1型向M2型转化从而抑制神经炎症反应,因此Tle具有一定的神经保护作用。 相似文献
2.
Ana Paula Valverde erson Camargo Ana L cia S Rodrigues 《World Journal of Psychiatry》2021,11(11):981-996
Major depressive disorder (MDD) is a disabling and highly prevalent mood disorder as well as a common cause of suicide. Chronic stress, inflammation, and intestinal dysbiosis have all been shown to play crucial roles in the patho physiology of MDD. Although conventional antidepressants are widely used in the clinic, they can take weeks to months to produce therapeutic effects. The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD. However, the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use. Therefore, agmatine, an endogenous glutamatergic modulator, has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway, similar to ketamine. However, recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota, which have been shown to play a crucial role in the pathophysiology of MDD, may also participate in the antidepressant-like effects of both ketamine and agmatine. This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies. Considering the anti-inflammatory properties of agmatine, it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state. Moreover, the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies. 相似文献
4.
Shafqat R. Chaudhry Ilana S. Lendvai Sajjad Muhammad Philipp Westhofen Johannes Kruppenbacher Lukas Scheef Henning Boecker Dirk Scheele Rene Hurlemann Thomas M. Kinfe 《Brain stimulation》2019,12(3):643-651
Objective
To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.Methods
This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls.Results
No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1β was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p?<?0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p?>?0.05]. No severe device-/stimulation-related adverse events occurred.Conclusion
2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1β plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics]. 相似文献5.
Estradiol, either from peripheral or central origin, activates multiple molecular neuroprotective and neuroreparative responses that, being mediated by estrogen receptors or by estrogen receptor independent mechanisms, are initiated at the membrane, the cytoplasm or the cell nucleus of neural cells. Estrogen-dependent signaling regulates a variety of cellular events, such as intracellular Ca2+ levels, mitochondrial respiratory capacity, ATP production, mitochondrial membrane potential, autophagy and apoptosis. In turn, these molecular and cellular actions of estradiol are integrated by neurons and non-neuronal cells to generate different tissue protective responses, decreasing blood-brain barrier permeability, oxidative stress, neuroinflammation and excitotoxicity and promoting synaptic plasticity, axonal growth, neurogenesis, remyelination and neuroregeneration. Recent findings indicate that the neuroprotective and neuroreparative actions of estradiol are different in males and females and further research is necessary to fully elucidate the causes for this sex difference. 相似文献
6.
7.
《Journal of pharmacological sciences》2020,142(3):116-123
Neutrophils constitute the major population of infiltrating leukocytes after stroke including intracerebral hemorrhage (ICH), and these cells may exhibit pro-inflammatory and anti-inflammatory phenotypes depending on the external stimuli. Here we constructed an experimental system to evaluate how the properties of neutrophils were influenced by the injured brain tissues. HL60 cells differentiated into neutrophils were added to the culture medium of neonatal rat cortico-striatal slices maintained at liquid–air interface. Thrombin was applied to the cultures to mimic the pathogenic events associated with ICH. HL60 cells responded to thrombin by increasing mRNA expression of pro-inflammatory IL-1β and anti-inflammatory IL-10 with a different time course. Co-presence of cortico-striatal slice cultures significantly enhanced IL-1β mRNA expression, whereas attenuated IL-10 mRNA expression, in HL60 cells. Toll-like receptor 4 (TLR4) agonist lipopolysaccharide synergistically enhanced IL-1β mRNA expression with thrombin, and TLR4 inhibitor TAK-242 abolished thrombin-induced IL-1β mRNA expression in the presence of slice cultures. On the other hand, thrombin-induced cell death in cortico-striatal cultures was attenuated by the presence of HL60 cells. This experimental system may provide a unique platform to elucidate complex cell-to-tissue interactions during ICH pathogenesis. 相似文献
8.
Major depressive disorder is a debilitating disorder affecting millions of people each year. Brain-derived neurotrophic factor (BDNF) and inflammation are two prominent biologic risk factors in the pathogenesis of depression that have received considerable attention. Many clinical and animal studies have highlighted associations between low levels of BDNF or high levels of inflammatory markers and the development of behavioral symptoms of depression. However, less is known about potential interaction between BDNF and inflammation, particularly within the central nervous system. Emerging evidence suggests that there is bidirectional regulation between these factors with important implications for the development of depressive symptoms and anti-depressant response. Elevated levels of inflammatory mediators have been shown to reduce expression of BDNF, and BDNF may play an important negative regulatory role on inflammation within the brain. Understanding this interaction more fully within the context of neuropsychiatric disease is important for both developing a fuller understanding of biological pathogenesis of depression and for identifying novel therapeutic opportunities. Here we review these two prominent risk factors for depression with a particular focus on pathogenic implications of their interaction. 相似文献
9.
《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2022,16(3):102444
Background and aimsThe negative impact of obesity on the brain is an issue of increasing clinical interest. Hence, this review summarized evidence linking obesity with brain morphology (gray and white matter volume), brain function (functional activation and connectivity), and cognitive function.MethodsA criticals review of the relevant published English articles between 2008 and 2022, using PubMed, Google Scholar and Science Direct. Studies were included if (1) an experimental/intervention study was conducted (2) the experiment/intervention included both high fat diet or body weight, whether it could counteract the negative effect brain morphological or functional change. Critical analysis for a supporting study was also carried out.ResultsBrain dysfunction can be recognized as result from neuroinflammation, oxidative stress, change in gut-brain hormonal functionality decrease regional blood flow or diminished hippocampal size and change in gut-brain hormonal functionality; which collectively translate into a cycle of deranged metabolic control and cognitive deficits, often obesity referred as changes in brain biochemistry and brain function. Recently, a few changes in brain structure and functions could be traced back even to obese children or adult. Evidence here suggested that obesity elicits early neuroinflammation effects, which likely disrupt the normal metabolism in hypothalamus, and hippocampus result from brain insulin resistance. The mechanisms of these robust effects are discussed herein.ConclusionBrain disease is inseparable from obesity itself and requires a better recognition to allow future therapeutic targeting for treatment of obesity. Additional research is needed to identify the best treatment targets and to identify if these changes reversible. 相似文献
10.
Cataloguing the effects of different types of stress on behaviour and physiology in rodent models has not been comprehensively attempted. Here, we systematically review whether chronic exposure to physical stress, psychosocial stress, or both types of stress can induce different behavioural and neurobiological outcomes in male and female rodents. We found that physical stress consistently increased depressive-like behaviour, impaired social interaction and decreased body weight, while psychosocial stress consistently increased both anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity, peripheral inflammation and microglial activation, and decreased hippocampal neurogenesis in male rodents. Moreover, we found that the combined effect of both stress types resulted in a more severe pathological state defined by increased anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity and central inflammation, and reduced hippocampal neurogenesis and neural plasticity in male rodents. Phenotypes for females were less consistent, irrespective of the type of stress exposure, on account of the limited number of studies using females. This review highlights that the type of stress may indeed matter and will help animal researchers to more appropriately choose a stress/depression model that fits their research purposes. 相似文献