Neuroimmunomodulation最新文献

{"title":"The Role of Immune Cell Subsets in the Development of Postoperative Cognitive Dysfunction in Surgical Patients Under Anesthesia.","authors":"Chao Ying, Feng Lin","doi":"10.1159/000548491","DOIUrl":"https://doi.org/10.1159/000548491","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) affects 10-54% of surgical patients, particularly elderly populations. This review discusses immune cell contributions to POCD pathogenesis through neuroinflammation mechanisms. While physiological postoperative inflammatory responses promote wound healing and tissue repair, pathological hyperactivation of immune pathways drives POCD development. Surgical trauma triggers systemic inflammation, disrupting blood-brain barrier integrity and facilitating immune cell infiltration. Innate immune cells, including activated microglia, infiltrating monocytes, and neutrophils, initiate neuroinflammatory cascades through cytokine release. Adaptive immune responses involve dysregulated T cell homeostasis with elevated Th17 cells and reduced regulatory T cells. Key molecular pathways include damage-associated molecular patterns, complement activation, and neurotrophin signaling disruption. Clinical biomarkers, particularly IL-6, TNF-α, and S100B, enable risk stratification with sensitivity ranging from 65-85% and specificity from 75-90%. Therapeutic strategies focus on immunomodulation through dexmedetomidine, anti-inflammatory agents, and perioperative optimization. Understanding these immune mechanisms provides foundations for targeted interventions to prevent this debilitating complication and improve perioperative cognitive outcomes.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-28"},"PeriodicalIF":2.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folliculostellate Cells at the Crossroads of Inflammation, Endocrine Regulation and Aging in the Pituitary Gland.","authors":"Florencia Herbstein, Julieta Reinoso, Nicolas Ciancio Del Giudice, David Gonilski-Pacin, Manuel Fiz, Joaquina Cagliero, Mariana Fuertes, Eduardo Arzt","doi":"10.1159/000548377","DOIUrl":"https://doi.org/10.1159/000548377","url":null,"abstract":"<p><p>Folliculostellate (FS) cells are non-endocrine cells of the anterior pituitary with roles in local communication, immune-endocrine regulation, and tissue homeostasis. Although they comprise only a small fraction of the gland, FS cells exert paracrine influence on hormone-secreting cells and respond to immune signals, particularly through interleukin-6 (IL-6) production. This review outlines classical and newly described features of FS cells and we also examine their dual role in pituitary tumorigenesis, where they may both promote and restrain tumor growth depending on context. FS cells act as immune sensors, mediating responses to bacterial signals and modulating the hypothalamic-pituitary-adrenal axis during stress and aging. Their potential contribution to inflammaging and tumor progression highlights FS cells as key players in pituitary physiology and pathology and immune-neuroendocrine connections.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-16"},"PeriodicalIF":2.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-immune-endocrine modulation of T-cell exhaustion in Central Nervous System parasitic diseases: insights from Toxoplasmosis and Neurocysticercosis.","authors":"Iván N Pérez-Osorio, Juan A Hernández-Aceves, José Alejandro Espinosa-Cerón, Rafael Saavedra, Gladis Fragoso, Edda Sciutto","doi":"10.1159/000548276","DOIUrl":"https://doi.org/10.1159/000548276","url":null,"abstract":"<p><p>Parasitic infections of the central nervous system (CNS) represent a considerable health burden in low- and middle-income countries. During chronic disease, parasites modulate host immunity to ensure long-term persistence while limiting collateral tissue damage. A key feature of this immune remodeling is the progressive T-cell dysfunction that may culminate in T-cell exhaustion, characterized by increased expression of inhibitory receptors (TIM-3, LAG-3, KLRG1), checkpoint molecules (PD-1, PD-L1), suppressor of cytokine signaling-1 (SOCS1), and arginase-1. This immune modulation is weakened by the neuroimmune endocrine (NIE) axis involving hormone release, cytokines, and neurotransmitters contributing to parasite survival. This review focuses on two parasitic CNS infections: Neurotoxoplasmosis (NT) induced by the intracellular protozoan Toxoplasma gondii and Neurocysticercosis (NCC) caused when cysticercus of the cestode Taenia solium lodge into the CNS. We present updated evidence on how these phylogenetically distant pathogens exploit the NIE network, describe the physiological consequences for the host, and highlight shared and distinct mechanisms behind T cell exhaustion. Finally, we address emerging immunotherapeutic strategies aimed at reversing exhaustion and restoring protective immunity.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-23"},"PeriodicalIF":2.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Damage on CNS cells elicited by innate immune activation: lessons to be learnt from the intracellular bacterium Brucella abortus.","authors":"Ana María Rodríguez, Julia Rodríguez, Alex D Guano, Guillermo H Giambartolomei","doi":"10.1159/000548181","DOIUrl":"https://doi.org/10.1159/000548181","url":null,"abstract":"<p><strong>Background: </strong>Devoid of a lymphatic system, the central nervous system (CNS) relies primarily on innate immunity for protection. While these immune responses help to fight pathogens, they can also cause irreversible damage because of the CNS's limited regenerative capacity. Therefore, it is crucial to understand which CNS cells contribute to pathogen clearance but in doing so potentially damage surrounding tissue.</p><p><strong>Summary: </strong>Neurobrucellosis, caused by intracellular bacteria from the genus Brucella, is an inflammatory disease. Recent studies have shown that astrocytes and microglia are the source of this neuro-inflammation. In response to Brucella infection they create a microenvironment in the CNS which leads to the destabilization of the glial structure, the damage of the blood-brain barrier (BBB) and neuronal demise. Using Brucella as an example, this review of CNS glial cells responses to an intracellular bacterium shows how inflammation generates damage on tissue instead of infection resolution.</p><p><strong>Key messages: </strong>Since the network of pathophysiological interactions described here are not necessarily limited to brucellosis, it is reasonable to assume that these mechanisms could be relevant in other neurological disorders in which inflammation plays a key role.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-24"},"PeriodicalIF":2.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation across the spectrum of neurodegenerative diseases: mechanisms and therapeutic frontiers.","authors":"Karyme M Alemán-Villa, David A Armienta-Rojas, Josué Camberos-Barraza, Ángel R Rábago-Monzón, Alejandro Camacho-Zamora, Juan F Osuna-Ramos, Javier A Magaña-Gómez, Alma M Guadrón-Llanos, Loranda Calderón-Zamora, Claudia D Norzagaray-Valenzuela, Marco A Valdez-Flores, Verónica J Picos-Cárdenas, Alberto K De la Herrán-Arita","doi":"10.1159/000548021","DOIUrl":"https://doi.org/10.1159/000548021","url":null,"abstract":"<p><p>Neuroinflammation has emerged as a central and dynamic component of the pathophysiology underlying a wide range of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Far from being a secondary consequence of neuronal damage, inflammatory processes (mediated by microglia, astrocytes, peripheral immune cells, and associated molecular mediators) actively shape disease onset, progression, and symptomatology. This review synthesizes current knowledge on the cellular and molecular mechanisms that govern neuroinflammatory responses, emphasizing both shared and disease-specific pathways. We examine how innate and adaptive immune interactions contribute to neuronal vulnerability and neurodegenerative cascades, and explore the reciprocal communication between systemic and central immune compartments. Particular attention is given to emerging therapeutic strategies aimed at modulating neuroinflammation, including immunomodulatory drugs, glial-targeted interventions, and novel delivery platforms. By integrating findings across disciplines and disease models, we outline key translational challenges and propose future directions to harness neuroinflammation as a therapeutic target in the era of precision medicine. Ultimately, a deeper understanding of neuroimmune dynamics holds promise for redefining both the diagnosis and treatment of neurodegenerative disorders.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-33"},"PeriodicalIF":2.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma IL-6 Levels as a Biomarker for Behavioral Changes in Alzheimer's Disease.","authors":"Fumihiko Yasuno, Atsushi Watanabe, Yasuyuki Kimura, Yumeka Yamauchi, Aya Ogata, Hiroshi Ikenuma, Junichiro Abe, Hiroyuki Minami, Takashi Nihashi, Kastunori Yokoi, Nobuyoshi Shimoda, Kensaku Kasuga, Takeshi Ikeuchi, Akinori Takeda, Takashi Sakurai, Kengo Ito, Takashi Kato","doi":"10.1159/000547726","DOIUrl":"10.1159/000547726","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-21"},"PeriodicalIF":2.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanocortin Receptor-Mediated Anti-Inflammatory Effect of Acthar® Gel in Human Myeloid Cells.","authors":"Kyle Hayes, Dale Wright","doi":"10.1159/000547302","DOIUrl":"https://doi.org/10.1159/000547302","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-11"},"PeriodicalIF":2.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Gut-Brain Axis in Modulating the Impact of Sterile Inflammation on Neuroimmune Responses in Neurodegenerative Diseases - Alzheimer's Disease and Parkinson's Disease.","authors":"Pei-Zhi Ling, Ka-Hing Wong, Yuen-Shan Ho, Wai-Yin Cheng, Raymond Chuen-Chung Chang","doi":"10.1159/000547746","DOIUrl":"https://doi.org/10.1159/000547746","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p><p><strong>Key messages: </strong>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.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-22"},"PeriodicalIF":2.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes and microRNA - a new form of remote and bidirectional neuroimmunomodulation?","authors":"Rainer H Straub","doi":"10.1159/000547243","DOIUrl":"https://doi.org/10.1159/000547243","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-70"},"PeriodicalIF":2.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Memoriam: Alfonse T. Masi, MD.","authors":"Maurizio Cutolo, Stefano Bombardieri, Rainer H Straub, Johannes W J Bijlsma, Frank Buttgereit","doi":"10.1159/000545633","DOIUrl":"10.1159/000545633","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"124-125"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}