Yile Zhou, Huihui Ju, Yan Hu, Tingting Li, Zhouyi Chen, Yuan Si, Xia Sun, Yi Shi, Hao Fang
OBJECTIVES: Enhanced neuroinflammation is an important mechanism underlying perioperative neurocognitive disorders. Regulatory T cells (Tregs) play a crucial role in regulating systemic immune responses. The present study was aimed to investigate the participation of Tregs in the development of postoperative cognitive dysfunction (POCD). METHODS: Surgery-associated neurocognitive disorder was induced in 18-month-old mice subjected to internal fixation of tibial fracture...
March 17, 2023: Journal of Neuroinflammation
Dongmei Gu, Luchun Wang, Nan Zhang, Huali Wang, Xin Yu
BACKGROUND: Naturally occurring antibodies (NAbs) are germline-encoded immunoglobulins that can bind to and clear out self-neo-epitopes as well as apoptotic and necrotic cells. However, NAbs pathological relevance in Alzheimer's disease (AD) is not well-understood. METHODS: Twenty-eight candidate proteins encoded by AD-associated genes were selected for this study based on a number of selection criteria, including preferential expression in the brain and B-lymphocyte cells...
March 15, 2023: Journal of Neuroinflammation
Marie-Kim St-Pierre, Micaël Carrier, Fernando González Ibáñez, Mohammadparsa Khakpour, Marie-Josée Wallman, Martin Parent, Marie-Ève Tremblay
The past decade has witnessed increasing evidence for a crucial role played by glial cells, notably astrocytes, in Alzheimer's disease (AD). To provide novel insights into the roles of astrocytes in the pathophysiology of AD, we performed a quantitative ultrastructural characterization of their intracellular contents and parenchymal interactions in an aged mouse model of AD pathology, as aging is considered the main risk factor for developing AD. We compared 20-month-old APP-PS1 and age-matched C57BL/6J male mice, among the ventral hippocampus CA1 strata lacunosum-moleculare and radiatum, two hippocampal layers severely affected by AD pathology...
March 14, 2023: Journal of Neuroinflammation
Mahima Kapoor, Subashchandrabose Chinnathambi
Microtubule-associated protein, Tau has been implicated in Alzheimer's disease for its detachment from microtubules and formation of insoluble intracellular aggregates within the neurons. Recent findings have suggested the expulsion of Tau seeds in the extracellular domain and their prion-like propagation between neurons. Transforming Growth Factor-β1 (TGF-β1) is a ubiquitously occurring cytokine reported to carry out immunomodulation and neuroprotection in the brain. TGF-β-mediated regulation occurs at the level of neuronal survival and differentiation, glial activation (astrocyte and microglia), amyloid production-distribution-clearance and neurofibrillary tangle formation, all of which contributes to Alzheimer's pathophysiology...
March 13, 2023: Journal of Neuroinflammation
Rachel Pei-Hsuan Wang, Jianpan Huang, Kannie Wai Yan Chan, Wai Keung Leung, Tetsuya Goto, Yuen-Shan Ho, Raymond Chuen-Chung Chang
BACKGROUND: Systemic activation of the immune system can exert detrimental effects on the central nervous system. Periodontitis, a chronic disease of the oral cavity, is a common source of systemic inflammation. Neuroinflammation might be a result of this to accelerate progressive deterioration of neuronal functions during aging or exacerbate pre-existing neurodegenerative diseases, such as Alzheimer's disease. With advancing age, the progressive increase in the body's pro-inflammatory status favors the state of vulnerability to both periodontitis and Alzheimer's disease...
March 13, 2023: Journal of Neuroinflammation
Anna Ballweg, Carolin Klaus, Letizia Vogler, Sabrina Katzdobler, Karin Wind, Artem Zatcepin, Sibylle I Ziegler, Birkan Secgin, Florian Eckenweber, Bernd Bohr, Alexander Bernhardt, Urban Fietzek, Boris-Stephan Rauchmann, Sophia Stoecklein, Stefanie Quach, Leonie Beyer, Maximilian Scheifele, Marcel Simmet, Emanuel Joseph, Simon Lindner, Isabella Berg, Norman Koglin, Andre Mueller, Andrew W Stephens, Peter Bartenstein, Joerg C Tonn, Nathalie L Albert, Tania Kümpfel, Martin Kerschensteiner, Robert Perneczky, Johannes Levin, Lars Paeger, Jochen Herms, Matthias Brendel
OBJECTIVES: Reactive gliosis is a common pathological hallmark of CNS pathology resulting from neurodegeneration and neuroinflammation. In this study we investigate the capability of a novel monoamine oxidase B (MAO-B) PET ligand to monitor reactive astrogliosis in a transgenic mouse model of Alzheimer`s disease (AD). Furthermore, we performed a pilot study in patients with a range of neurodegenerative and neuroinflammatory conditions. METHODS: A cross-sectional cohort of 24 transgenic (PS2APP) and 25 wild-type mice (age range: 4...
March 11, 2023: Journal of Neuroinflammation
Xiao-Yu Yin, Xiao-Hui Tang, Shi-Xu Wang, Yong-Chang Zhao, Min Jia, Jian-Jun Yang, Mu-Huo Ji, Jin-Chun Shen
BACKGROUND: Microglial activation-mediated neuroinflammation is one of the essential pathogenic mechanisms of sepsis-associated encephalopathy (SAE). Mounting evidence suggests that high mobility group box-1 protein (HMGB1) plays a pivotal role in neuroinflammation and SAE, yet the mechanism by which HMGB1 induces cognitive impairment in SAE remains unclear. Therefore, this study aimed to investigate the mechanism of HMGB1 underlying cognitive impairment in SAE. METHODS: An SAE model was established by cecal ligation and puncture (CLP); animals in the sham group underwent cecum exposure alone without ligation and perforation...
March 11, 2023: Journal of Neuroinflammation
Lingzhi Li, Ziping Han, Rongliang Wang, Junfen Fan, Yangmin Zheng, Yuyou Huang, Zhenhong Yang, Feng Yan, Ping Liu, Haiping Zhao, Qingfeng Ma, Yumin Luo
BACKGROUND: Neutrophil serine proteinases (NSPs), released by activated neutrophils, are key proteins involved in the pathophysiologic processes of stroke. NSPs are also implicated in the process and response of thrombolysis. This study aimed to analyze three NSPs (neutrophil elastase, cathepsin G, and proteinase 3) in relation to acute ischemic stroke (AIS) outcomes and in relation to the outcomes of patients treated with intravenous recombinant tissue plasminogen activator (IV-rtPA)...
March 11, 2023: Journal of Neuroinflammation
Esteban Palacios, Lorena Lobos-González, Simón Guerrero, Marcelo J Kogan, Baohai Shao, Jay W Heinecke, Andrew F G Quest, Lisette Leyton, Manuel Valenzuela-Valderrama
BACKGROUND: Helicobacter pylori (Hp) infects the stomach of 50% of the world's population. Importantly, chronic infection by this bacterium correlates with the appearance of several extra-gastric pathologies, including neurodegenerative diseases. In such conditions, brain astrocytes become reactive and neurotoxic. However, it is still unclear whether this highly prevalent bacterium or the nanosized outer membrane vesicles (OMVs) they produce, can reach the brain, thus affecting neurons/astrocytes...
March 9, 2023: Journal of Neuroinflammation
Michael R Grovola, Catherine von Reyn, David J Loane, D Kacy Cullen
Traumatic brain injury (TBI) often results in prolonged or permanent brain dysfunction with over 2.8 million affected annually in the U.S., including over 56,000 deaths, with over 5 million total survivors exhibiting chronic deficits. Mild TBI (also known as concussion) accounts for over 75% of all TBIs every year. Mild TBI is a heterogeneous disorder, and long-term outcomes are dependent on the type and severity of the initial physical event and compounded by secondary pathophysiological consequences, such as reactive astrocytosis, edema, hypoxia, excitotoxicity, and neuroinflammation...
March 9, 2023: Journal of Neuroinflammation
Min Chu, Lulu Wen, Deming Jiang, Li Liu, Haitian Nan, Ailing Yue, Yingtao Wang, Yihao Wang, Miao Qu, Ningqun Wang, Liyong Wu
BACKGROUND: Neuroinflammation plays a significant role in the progression of frontotemporal dementia (FTD). However, the association between peripheral inflammatory factors and brain neurodegeneration is poorly understood. We aimed to examine changes in peripheral inflammatory markers in patients with behavioural variant FTD (bvFTD) and explore the potential association between peripheral inflammation and brain structure, metabolism, and clinical parameters. METHODS: Thirty-nine bvFTD patients and 40 healthy controls were enrolled and underwent assessment of plasma inflammatory factors, positron emission tomography/magnetic resonance imaging, and neuropsychological assessments...
March 8, 2023: Journal of Neuroinflammation
Pan Cui, Wanting Lu, Junjie Wang, Fei Wang, Xiyue Zhang, Xiaodan Hou, Fang Xu, Yan Liang, Guoliang Chai, Junwei Hao
Vitamin D deficiency is associated with worse clinical outcomes after ischemic stroke; nevertheless, the pathophysiological mechanisms remain largely unexplored. In this study, we characterized the molecular mechanisms of how vitamin D signaling modulated stroke progression in male mouse ischemia-reperfusion stroke models. We found that vitamin D receptor (VDR) exhibited a predominant upregulation in peri-infarct microglia/macrophages following cerebral ischemia. Conditional Vdr inactivation in microglia/macrophages markedly augmented infarct volumes and neurological deficits...
March 8, 2023: Journal of Neuroinflammation
Grégoire Stym-Popper, Karen Matta, Thomas Chaigneau, Roshan Rupra, Alexandros Demetriou, Stéphane Fouquet, Cira Dansokho, Cécile Toly-Ndour, Guillaume Dorothée
BACKGROUND: Increasing evidence supports a key role for peripheral immune processes in the pathophysiology of Alzheimer's disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate and adaptive peripheral immune effectors. We previously showed that regulatory T cells (Tregs) have a beneficial impact on disease progression in AD-like pathology, notably by modulating the microglial response associated with Aβ deposits in a mouse model of amyloid pathology...
March 8, 2023: Journal of Neuroinflammation
Marina McDew-White, Eunhee Lee, Lakmini S Premadasa, Xavier Alvarez, Chioma M Okeoma, Mahesh Mohan
BACKGROUND: Although the advent of combination anti-retroviral therapy (cART) has transformed HIV into a manageable chronic disease, an estimated 30-50% of people living with HIV (PLWH) exhibit cognitive and motor deficits collectively known as HIV-associated neurocognitive disorders (HAND). A key driver of HAND neuropathology is chronic neuroinflammation, where proinflammatory mediators produced by activated microglia and macrophages are thought to inflict neuronal injury and loss. Moreover, the dysregulation of the microbiota-gut-brain axis (MGBA) in PLWH, consequent to gastrointestinal dysfunction and dysbiosis, can lead to neuroinflammation and persistent cognitive impairment, which underscores the need for new interventions...
March 8, 2023: Journal of Neuroinflammation
Suelen Silva Gomes Dias, Tamires Cunha-Fernandes, Luciana Souza-Moreira, Vinicius Cardoso Soares, Giselle Barbosa Lima, Isaclaudia G Azevedo-Quintanilha, Julia Santos, Filipe Pereira-Dutra, Caroline Freitas, Patricia A Reis, Stevens Kastrup Rehen, Fernando A Bozza, Thiago M Lopes Souza, Cecilia J G de Almeida, Patricia T Bozza
Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs)...
March 8, 2023: Journal of Neuroinflammation
Macarena S Aloi, Katherine E Prater, Raymond E A Sánchez, Asad Beck, Jasmine L Pathan, Stephanie Davidson, Angela Wilson, C Dirk Keene, Horacio de la Iglesia, Suman Jayadev, Gwenn A Garden
Alzheimer's Disease (AD) is characterized by the accumulation of extracellular amyloid-β (Aβ) as well as CNS and systemic inflammation. Microglia, the myeloid cells resident in the CNS, use microRNAs to rapidly respond to inflammatory signals. MicroRNAs (miRNAs) modulate inflammatory responses in microglia, and miRNA profiles are altered in Alzheimer's disease (AD) patients. Expression of the pro-inflammatory miRNA, miR-155, is increased in the AD brain. However, the role of miR-155 in AD pathogenesis is not well-understood...
March 7, 2023: Journal of Neuroinflammation
Shah Tauseef Bashir, Catherine R Redden, Kishori Raj, Rachel B Arcanjo, Sandra Stasiak, Quanxi Li, Andrew J Steelman, Romana A Nowak
BACKGROUND: Chronic pelvic pain (CPP) is a common symptom of endometriosis. Women with endometriosis are also at a high risk of suffering from anxiety, depression, and other psychological disorders. Recent studies indicate that endometriosis can affect the central nervous system (CNS). Changes in the functional activity of neurons, functional magnetic resonance imaging signals, and gene expression have been reported in the brains of rat and mouse models of endometriosis. The majority of the studies thus far have focused on neuronal changes, whereas changes in the glial cells in different brain regions have not been studied...
March 6, 2023: Journal of Neuroinflammation
Melanie Bühler, Dandan Li, Lin Li, Sandra Runft, Inken Waltl, Andreas Pavlou, Ulrich Kalinke, Malgorzata Ciurkiewicz, Jochen Huehn, Stefan Floess, Andreas Beineke, Wolfgang Baumgärtner, Ingo Gerhauser
BACKGROUND: Theiler's murine encephalomyelitis virus (TMEV) is a single-stranded RNA virus that causes encephalitis followed by chronic demyelination in SJL mice and spontaneous seizures in C57BL/6 mice. Since earlier studies indicated a critical role of type I interferon (IFN-I) signaling in the control of viral replication in the central nervous system (CNS), mouse strain-specific differences in pathways induced by the IFN-I receptor (IFNAR) might determine the outcome of TMEV infection...
March 5, 2023: Journal of Neuroinflammation
María Vargas-Soria, Mónica García-Alloza, Miriam Corraliza-Gómez
Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded by a prediabetic state. The excess of blood glucose can damage multiple organs, including the brain. In fact, cognitive decline and dementia are increasingly being recognized as important comorbidities of diabetes. Despite the largely consistent link between diabetes and dementia, the underlying causes of neurodegeneration in diabetic patients remain to be elucidated. A common factor for almost all neurological disorders is neuroinflammation, a complex inflammatory process in the central nervous system for the most part orchestrated by microglial cells, the main representatives of the immune system in the brain...
March 3, 2023: Journal of Neuroinflammation
Xiao Cheng, Li Chi, Tianqiong Lin, Fengyin Liang, Zhong Pei, Jianbo Sun, Wei Teng
BACKGROUND: Periodontitis is closely associated with the pathogenesis of Alzheimer's disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, has been reported in our recent study to cause immune-overreaction and induce cognitive impairment. Monocytic myeloid-derived suppressor cells (mMDSCs) possess potent immunosuppressive function. It is unclear whether mMDSCs-mediated immune homeostasis is impaired in AD patients with periodontitis, and whether exogenous mMDSCs could ameliorate immune-overreaction and cognitive impairment induced by Pg...
March 2, 2023: Journal of Neuroinflammation
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