Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

CNS Neuroscience & Therapeutics, Год журнала: 2020, Номер 27(1), С. 36 - 47

Опубликована: Дек. 30, 2020

Abstract The blood–brain barrier (BBB) is an important physiological that separates the central nervous system (CNS) from peripheral circulation, which contains inflammatory mediators and immune cells. BBB regulates cellular molecular exchange between blood vessels brain parenchyma. Normal functioning of crucial for homeostasis proper function brain. It has been demonstrated inflammation can disrupt by various pathways, resulting in different CNS diseases. Recently, clinical research also showed complications following SARS‐CoV‐2 infection chimeric antigen receptor (CAR)‐T cell therapy, both lead to a cytokine storm circulation. Therefore, elucidation mechanisms underlying disruption induced will provide basis protecting context exacerbated In present review, we first summarize properties makes immune‐privileged organ. We then discuss relevance inflammation‐induced Finally, elaborate factors BBB.

Язык: Английский

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Role of sleep deprivation in immune-related disease risk and outcomes

Communications Biology, Год журнала: 2021, Номер 4(1)

Опубликована: Ноя. 18, 2021

Modern societies are experiencing an increasing trend of reduced sleep duration, with nocturnal sleeping time below the recommended ranges for health. Epidemiological and laboratory studies have demonstrated detrimental effects deprivation on Sleep exerts immune-supportive function, promoting host defense against infection inflammatory insults. has been associated alterations innate adaptive immune parameters, leading to a chronic state increased risk infectious/inflammatory pathologies, including cardiometabolic, neoplastic, autoimmune neurodegenerative diseases. Here, we review recent advancements responses as evidenced by experimental epidemiological studies, pathophysiology, role deprivation-induced changes in Gaps knowledge methodological pitfalls still remain. Further understanding causal relationship between deregulation would help identify individuals at disease prevent adverse health outcomes.

Язык: Английский

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Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Март 5, 2022

The implication of gut microbiota in the control brain functions health and disease is a novel, currently emerging concept. Accumulating data suggest that exert its action at least part by modulating neuroinflammation. Given link between neuroinflammatory changes neuronal activity, it plausible may affect indirectly impacting microglia, key player Indeed, increasing evidence suggests interplay microglia synaptic dysfunction involve microbiota, among other factors. In addition to these indirect microglia-dependent actions on has been recently recognized could also activity directly stimulation vagus nerve.

Язык: Английский

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Blood–Brain Barrier Breakdown: An Emerging Biomarker of Cognitive Impairment in Normal Aging and Dementia

Frontiers in Neuroscience, Год журнала: 2021, Номер 15

Опубликована: Авг. 19, 2021

The blood-brain barrier (BBB) plays a vital role in maintaining the specialized microenvironment of neural tissue. It separates peripheral circulatory system from brain parenchyma while facilitating communication. Alterations distinct physiological properties BBB lead to breakdown associated with normal aging and various neurodegenerative diseases. In this review, we first briefly discuss process, then review phenotypes mechanisms that further cause neurodegeneration cognitive impairments. We also summarize dementia such as Alzheimer's disease (AD) vascular (VaD) subsequently disruption correlated cognition decline. Overlaps between AD VaD are discussed. Techniques could identify biomarkers summarized. Finally, concluded be used an emerging biomarker assist diagnose impairment dementia.

Язык: Английский

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Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies

Journal of Experimental & Clinical Cancer Research, Год журнала: 2021, Номер 40(1)

Опубликована: Ноя. 18, 2021

Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR products have been approved by the US Food Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to development of therapy, most notably cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity (ICANS). Understanding mechanisms underlying these establishing prevention strategies are important. In this review, we summarize CRS ICANS provide potential strategies.

Язык: Английский

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Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients

Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)

Опубликована: Янв. 20, 2022

Abstract Background Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. Objective To analyze systematically CSF COVID-19. Methods Retrospective analysis of 150 lumbar punctures 127 PCR-proven symptoms seen at 17 European university centers Results The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72–50.8]), which present 58/116 (50%) samples without pre-/coexisting CNS diseases (group I). remained elevated > 14d (47.6%) even 30d (55.6%) after onset. total protein 54/118 (45.8%) 65.35 mg/dl [45.3–240.4]) strongly correlated QAlb. white cell count (WCC) increased 14/128 (11%) (mostly lympho-monocytic; median 10 cells/µl, 100 only 4). An albuminocytological dissociation (ACD) found 43/115 (37.4%) samples. l -lactate 26/109 (24%; 3.04 mmol/l [2.2–4]). CSF-IgG 50/100 (50%), but peripheral origin, since QIgG normal almost all cases, as were QIgA QIgM. In 58/103 (56%) pattern 4 oligoclonal bands (OCB) compatible systemic inflammation present, while CSF-restricted OCB 2/103 (1.9%). SARS-CoV-2-CSF-PCR negative 76/76 Routine findings 35%. Cytokine levels frequently (often associated BCB dysfunction) serum, partly remaining positive high for weeks/months (939 tests). Of note, a SARS-CoV-2-IgG-antibody index (AI) 2/19 (10.5%) unusually WCC both them interleukin-6 (IL-6) one (not tested other). Anti-neuronal/anti-glial autoantibodies mostly absent serum (1509 disorders II [ N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, lymphoma, anti-Yo subarachnoid hemorrhage), representative respective disease. Conclusions is mainly characterized by disruption absence intrathecal inflammation, endotheliopathy. Persistent cytokine may contribute to acute ‘long COVID’. Direct infection SARS-CoV-2, if occurring all, seems be rare. Broad differential diagnostic considerations recommended avoid misinterpretation treatable coexisting complications

Язык: Английский

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The Glymphatic System (En)during Inflammation

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(14), С. 7491 - 7491

Опубликована: Июль 13, 2021

The glymphatic system is a fluid-transport that accesses all regions of the brain. It facilitates exchange cerebrospinal fluid and interstitial clears waste from metabolically active Astrocytic endfeet their dense expression aquaporin-4 water channels promote between perivascular spaces neuropil. Cerebrospinal fluids are together transported back to vascular compartment by meningeal cervical lymphatic vessels. Multiple lines work show neurological diseases in general impair transport. Insofar as plays pseudo-lymphatic role central nervous system, it poised play neuroinflammation. In this review, we discuss how association with vessel calls for renewal established concepts on CNS an immune-privileged site. We also potential approaches target combat

Язык: Английский

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Mechanisms of Blood–Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids

Cells, Год журнала: 2023, Номер 12(4), С. 657 - 657

Опубликована: Фев. 18, 2023

Impairment of the blood-brain barrier (BBB) integrity is implicated in numerous neurological disorders associated with neuroinflammation, neurodegeneration and aging. It now evident that short-chain fatty acids (SCFAs), mainly acetate, butyrate propionate, produced by anaerobic bacterial fermentation dietary fiber intestine, have a key role communication between gastrointestinal tract nervous system are critically important for preservation BBB under different pathological conditions. The effect SCFAs on improvement compromised based decrease paracellular permeability via restoration junctional complex proteins affecting their transcription, intercellular localization or proteolytic degradation. This review focused revealed putative underlying mechanisms direct indirect effects function brain endothelial cells. We consider G-protein-coupled receptor-mediated SCFAs, SCFAs-stimulated acetylation histone non-histone inhibition deacetylases, crosstalk these signaling pathways transcriptional factors NF-κB Nrf2 as mainstream SCFA's integrity.

Язык: Английский

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Perioperative neurocognitive disorders: A narrative review focusing on diagnosis, prevention, and treatment

CNS Neuroscience & Therapeutics, Год журнала: 2022, Номер 28(8), С. 1147 - 1167

Опубликована: Июнь 1, 2022

Abstract Perioperative neurocognitive disorders (NCDs) refer to abnormalities detected during the perioperative periods, including preexisting cognitive impairment, preoperative delirium, delirium occurring up 7 days after surgery, delayed recovery, and postoperative NCD. The Diagnostic Statistical Manual of Mental Disorders‐5th edition (DSM‐5) is golden standard for diagnosing NCDs. Given impracticality using DSM‐5 by non‐psychiatric practitioners, many diagnostic tools have been developed validated different clinical scenarios. etiology NCDs multifactorial includes predisposing precipitating factors. Identifying these risk factors conducive stratification reduction. Prevention should include avoiding possible contributors implementing nonpharmacologic pharmacological interventions. former generally benzodiazepines, anticholinergics, prolonged liquid fasting, deep anesthesia, cerebral oxygen desaturation, intraoperative hypothermia. Nonpharmacologic measures prehabilitation, comprehensive geriatric assessment, fast‐track combined use regional block, sleep promotion. Pharmacological dexmedetomidine, nonsteroidal anti‐inflammatory drugs, acetaminophen are found beneficial effects. Nonpharmacological treatments first‐line established still limited severely agitated or distressed patients.

Язык: Английский

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Inflammation context in Alzheimer’s disease, a relationship intricate to define

Biological Research, Год журнала: 2022, Номер 55(1)

Опубликована: Дек. 23, 2022

Abstract Alzheimer’s disease (AD), the most common form of dementia, is characterized by accumulation amyloid β (Aβ) and hyperphosphorylated tau protein aggregates. Importantly, Aβ species are able to activate astrocytes microglia, which release several proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) interleukin 1β (IL-1β), together with reactive oxygen (ROS) nitrogen (RNS), triggering neuroinflammation. However, this inflammatory response has a dual function: it can play protective role increasing degradation clearance, but also contribute overproduction induce neurodegeneration synaptic loss. Due significant inflammation in pathogenesis AD, mediators have been proposed AD markers, TNF-α, IL-1β, Iba-1, GFAP, NF-κB, TLR2, MHCII. use anti-inflammatory drugs NSAIDs emerged potential treatment against AD. Moreover, diseases related systemic or local inflammation, including infections, cerebrovascular accidents, obesity, risk factors for development In following review, we focus on key processes associated pathogenesis.

Язык: Английский

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