Neuroimmunomodulation最新文献

Introduction: Behavioral and psychological symptoms of dementia (BPSD) significantly affect the quality of life for patients with Alzheimer's disease (AD) and contribute to caregiver burden. Although systemic inflammation is implicated in AD pathophysiology, the specific role of peripheral immune activity-particularly interleukin-6 (IL-6)-in relation to BPSD remains unclear, especially regarding its independent effects from central neuroinflammation.

Methods: We conducted a cross-sectional study of 23 biomarker-confirmed patients diagnosed with AD or prodromal AD. Plasma and cerebrospinal fluid (CSF) levels of IL-6, IL-1β, TNF-α, and C-reactive protein (CRP) were measured. BPSD was assessed using the Dementia Behavior Disturbance (DBD) scale. Central neuroinflammation was quantified via 11C-DPA-713 translocator protein positron emission tomography (TSPO-PET). Stepwise multiple linear regression and Bayesian analyses were used to identify predictors of BPSD severity.

Results: Plasma IL-6 emerged as the only significant predictor of DBD scores in frequentist and Bayesian regression models. Other demographic, cognitive, and inflammatory variables, including CSF IL-6 and TSPO-PET binding, showed no significant association with behavioral symptoms. No correlation was observed between plasma and CSF IL-6 levels, nor between plasma IL-6 and TSPO-PET measures.

Conclusion: Peripheral IL-6 is significantly associated with BPSD severity in AD, independently of central inflammatory markers. This finding suggests a distinct peripheral immune mechanism underlying neuropsychiatric symptoms, potentially mediated through systemic pathways such as vagus nerve signaling or gut-brain-immune interactions. Peripheral IL-6 may serve as a clinically relevant biomarker and therapeutic target for behavioral disturbances in AD.

Introduction Acthar® Gel, a complex mixture of porcine adrenocorticotropic hormone analogs that activates all 5 melanocortin receptor (MCR) subtypes, is an approved noncorticosteroid treatment for multiple sclerosis (MS) exacerbations. Methods MCR expression and anti-inflammatory effects of Acthar Gel in human monocyte-derived macrophages and human brain-derived microglia were investigated following lipopolysaccharide stimulation in vitro. Results Melanocortin receptor 1 was expressed at substantially higher levels than the other MCR subtypes in human monocyte-derived macrophages (MDMs) and was the only MCR gene detected in human adult microglia. As shown by microarray gene expression analysis, polarization of MDMs to a proinflammatory phenotype increased the expression and secretion of interleukin-6, tumor necrosis factor α, and CXC motif chemokine ligand 10, which were inhibited in a dose-dependent manner with Acthar Gel treatment. Conclusions These results are consistent with previous insights that Acthar Gel has an immunomodulatory mechanism distinct from glucocorticoids alone and suggest that Acthar Gel can improve clinical outcomes in MS and other inflammation-mediated central nervous system disorders by inhibiting multiple proinflammatory cytokine signaling pathways.

Background: Emerging evidence has demonstrated the important role of gut microbiota in host physiology, affecting host immunity. The gut-brain axis has been identified between the central nervous system and the gut microbiota, indicating bidirectional communication between the two systems.

Summary: Microbial imbalance (in other words, gut dysbiosis) can lead to chronic systemic inflammation, resulting in neuroinflammation as an example of sterile inflammation. Three major pathways in causing neuroinflammation from chronic systemic inflammation by the gut microbiota via the gut-brain axis are discussed throughout the article. This includes the inflammasome signaling, altered permeability of the blood-brain barrier by the short-chain fatty acids (SCFAs), and oxidative stress.

Key messages: Through understanding that gut dysbiosis is capable of modulating neuroinflammation, the use of probiotics in neurodegenerative diseases can be investigated to assess their therapeutic potential. Increasing clinical studies show positive results on the use of probiotics in neurodegenerative diseases, yet further evidence is required to validate their clinical effectiveness.

Background: There exists the well-known crosstalk between brain and immune system, which has much to do with energy regulation in the body. The selfish brain dominates energy distribution in the presence of threats like predators, wounding with haemorrhage, food scarcity, thirst, cold, and heat. The selfish immune system dominates energy allocation during infection and wounding with infection. Often, the two major organ systems selfishly inhibit each other to govern energy self-supply. However, sometimes they can help each other in early situation with threats (immediate mutual assistance). The brain influences the immune system by means of hard-wired nerve fibres and their neurotransmitters and through hormones from brain-controlled endocrine glands. The immune system influences structures of the brain through soluble factors like cytokines, migrating immune cells, and solute receptors (e.g., of cytokines) on sensory nerve fibres. After the appearance of microRNA, this classical view of neuroimmunomodulation needs some revision.

Summary: This view of neuroimmunomodulation has recently been expanded by experimental work in stress research [1, 2]. Next to classical connectors of brain and immune system, exosome microRNA may play an outstanding role in this bidirectional crosstalk. This review systematically analyses sources of microRNA in the brain and effects of this microRNA on target immune function. Vice versa, microRNA of distinct immune cells are demonstrated how they might interfere with various brain functions. Messages: This review has the character of a theory that should stimulate new research in order to define - in a single publication - the origin of microRNA in the brain and its influence on the target in immune cells and vice versa. The field of neuroimmunomodulation should include these new microRNA pathways to obtain a full picture of bidirectional interactions between the two selfish organ systems.

Introduction: Major depressive disorder (MDD) significantly impacts millions worldwide, with limited success in achieving remission for many patients, leading to high disease burden and increased suicide risk. Psychotherapy and antidepressants, although effective, do not provide relief for all, prompting the search for alternative treatments. Ketogenic diets have demonstrated positive effects on brain health. Our study aims to investigate the efficacy of the ketogenic diet in alleviating MDD symptoms, filling a critical gap in psychiatric treatment options and offering a novel dietary approach with potential to mitigate disease burden and enhance mental well-being.

Methods: This phase 2 randomized controlled trial will evaluate the efficacy of a 10-week program of dietitian counseling and ketogenic meal provision versus an intervention with similar dietetic contact promoting a healthy, insulin-lowering, non-ketogenic diet. The primary outcome is the change in the Patient Health Questionnaire nine-item depression score. Secondary outcomes include cognitive and affective mindfulness, self-efficacy, sleep, cognitive function, work and social adjustment, and various immunological, metabolic, and microbiome markers at weeks 6 and 10.

Conclusion: This study addresses a critical gap in depression treatment by exploring the ketogenic diet's potential as a metabolic mood enhancing intervention. Given the global impact of depression and limitations of current therapies, this research is valuable for exploring previously underappreciated neuroprotective and metabolic mechanisms and clinical benefits.

Introduction: The aim of this study was to investigate the correlation between serum NLRP1 inflammasome level and depressive state in acute stage of stroke.

Methods: A total of 102 patients with acute stroke who were hospitalized for the first time in the Department of Neurology of the First Affiliated Hospital of Dali University from April 2023 to October 2023 were included, and 80 of them met the inclusion criteria. On the 7th day of admission, the patients were evaluated using the 24-item Hamilton Depression Scale (HAMD-24) and were divided into 31 patients in the acute stage of stroke depression group and 49 patients in the acute stage of stroke non-depression group. The general clinical data of patients were collected, the unified Stroke Scale score (NIHSS) and Pittsburgh Sleep Quality Index score (PSQI) were performed, and fasting serum was collected at 8 a.m. the next morning. NLRP1 inflammatory bodies (NLRP1, ASC, Caspase1) and inflammatory factors IL-1β, IL-18, IL-10, tumor necrosis factor (TNF)-α were detected.

Results: (1) The incidence of depression in acute stage of stroke was 38.75%. (2) There were statistically significant differences in PSQI and NIHSS scores between the two groups (p < 0.05), and the scores were correlated with the degree of depression, and were positively correlated with HAMD-24 scores (p < 0.05). (3) The expression levels of NLRP1, IL-18, and TNF-α in serum were significantly different between the two groups (p < 0.01), and the expression levels were correlated with the degree of depression, and were positively correlated with HAMD-24 scores (p < 0.05). There were no significant differences in the expression levels of serum IL-1β, IL-10, Caspase-1 and ASC (p > 0.05). (4) Further analysis by stepwise fitting binary logistic regression showed that NIHSS score, NLRP1, and IL-18 level were independent risk factors for depression in acute stage of stroke (p < 0.05). (5) NIIHSS score, NLRP1, and IL-18 receiver operating characteristic curve area have certain predictive value for the occurrence and development of acute depression during stroke.

Conclusion: The more severe the neurological impairment and sleep disorder, the higher the expression level of NLRP1 inflammasome in blood, and the more severe the depression in acute stage of stroke.

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Background: Chronic Chagas disease can affect multiple organs, most notably the heart and gastrointestinal tract, and in some cases, the nervous system. However, the underlying pathophysiological mechanisms of this parasitic infection remain incompletely understood. Summary: Evidence from studies in both mice with acute Trypanosoma cruzi (T. cruzi) infection and in patients with Chagas disease has revealed a range of immune-neuroendocrine alterations and metabolic disruptions. In this review, we highlight key findings in human Chagas disease related to these abnormalities and discuss their potential contributions to disease pathogenesis. Key Messages: In the context of chronic Chagas disease, the neuroendocrine-immune axis operates as a dynamic interface, integrating systemic immune-endocrine processes with localized responses in the central nervous system (CNS), with each component influencing disease advancement and organ-specific pathology through distinct yet interconnected mechanisms.