Blood-brain barrier disruption: a culprit of cognitive decline?

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 7, 2024

Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also systemic diseases, which seriously influence the quality life and expectancy patients. As highly selective anatomical functional interface between circulation, blood-brain barrier (BBB) plays pivotal role in maintaining homeostasis normal function. The pathogenesis underlying cognitive may vary, nevertheless, accumulating evidences support BBB disruption as most prevalent contributing factor. This mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress excitotoxicity. However, direct evidence showing that causes is scarce, interestingly, manipulation opening alone exert beneficial or detrimental neurological effects. A overview present literature shows close relationship decline, risk factors disruption, well cellular molecular mechanisms disruption. Additionally, we discussed possible leading by potential therapeutic strategies prevent enhance repair. review aims foster more investigations on early diagnosis, effective therapeutics, rapid restoration against would yield better outcomes patients with dysregulated function, although their causative has yet been completely established.

Language: Английский

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An Alternative Mode of GPCR Transactivation: Activation of GPCRs by Adhesion GPCRs

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 552 - 552

Published: Jan. 10, 2025

G protein-coupled receptors (GPCRs), critical for cellular communication and signaling, represent the largest cell surface protein family play important roles in numerous pathophysiological processes. Consequently, GPCRs have become a primary focus drug discovery efforts. Beyond their traditional protein-dependent signaling pathways, are also capable of activating alternative mechanisms, including protein-independent biased crosstalk. A particularly novel mode employed by these is GPCR transactivation, which enables cross-communication between other receptor types. Intriguingly, transactivation distinct has been identified. In this review, I provide an overview known mechanisms explore recently uncovered mediated adhesion-class (aGPCRs). These aGPCR-GPCR processes regulate unique type-specific functions, offering exciting opportunity to develop therapies that precisely modulate specific GPCR-mediated biological effects.

Language: Английский

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Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(7), P. 1158 - 1171

Published: June 20, 2024

Language: Английский

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Compromised endothelial Wnt/β-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Oct. 19, 2024

The blood-brain barrier (BBB) is a critical interface that maintains the central nervous system homeostasis by controlling exchange of substances between blood and brain. Disruption BBB plays vital role in development neuroinflammation neurological dysfunction sepsis, but mechanisms which becomes disrupted during sepsis are not well understood. Here, we induced endotoxemia, major type mice intraperitoneal injection lipopolysaccharide (LPS). LPS acutely increased permeability, activated microglia, heightened inflammatory responses brain endothelium parenchyma. Concurrently, or proinflammatory cytokines NF-κB pathway, inhibiting Wnt/β-catenin signaling endothelial cells vitro vivo. Cell culture study revealed p65 directly interacted with β-catenin to suppress signaling. Pharmacological pathway inhibition restored activity mitigated disruption septic mice. Furthermore, genetic pharmacological activation substantially alleviated LPS-induced leakage neuroinflammation, while conditional ablation Wnt7a/7b co-receptor Gpr124 exacerbated caused LPS. Mechanistically, rectified reduced expression levels tight junction protein ZO-1 transcytosis suppressor Mfsd2a both paracellular transcellular permeability BBB. Our findings demonstrate endotoxemia-associated systemic inflammation decreases through activating resulting acute neuroinflammation. Targeting may offer promising therapeutic strategy for preserving integrity treating sepsis.

Language: Английский

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Animal models of Long Covid: A hit-and-run disease

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(773)

Published: Nov. 13, 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because emergence variants that can cause disease 2019 (COVID-19) or enhance Long Covid phenotypes. About 5 to 10% SARS-CoV-2-infected individuals develop Covid, which, similar COVID 19, often affects lung. However, also affect other peripheral organs, especially brain. causal relationships between phenotypes, long-term symptoms, involvement multiple organ systems elusive, animal model mimicking both post-acute phases are imperative. Here, we review current state models, including possible future applications.

Language: Английский

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Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19

Viruses, Journal Year: 2025, Volume and Issue: 17(1), P. 98 - 98

Published: Jan. 14, 2025

Post-acute sequelae of COVID-19 (PASC) are a diverse set symptoms and syndromes driven by dysfunction multiple organ systems that can persist for years negatively impact the quality life millions individuals. We currently lack specific therapeutics patients with PASC, due in part to an incomplete understanding its pathogenesis, especially non-pulmonary sequelae. Here, we discuss three animal models have been utilized investigate PASC: non-human primates (NHPs), hamsters, mice. focus on neurological, gastrointestinal, cardiovascular PASC highlight advances mechanistic insight made using these models, as well discussing warrant continued intensive research.

Language: Английский

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Linear association between high-sensitivity C-reactive protein and postoperative delirium after general anesthesia: a cross-sectional study

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 31, 2025

To investigate the association between high-sensitivity C-reactive protein (Hs-CRP) levels and risk of postoperative delirium (POD) following general anesthesia. This retrospective cross-sectional study included 644 patients who underwent Univariate multivariate logistic regression analyses were performed to evaluate relationship Hs-CRP POD, with subgroup used assess stratified associations. Receiver operator characteristic (ROC) curve analysis was employed predictive efficacy for POD. Restricted cubic spline (RCS) conducted explore linear log-transformed (Log10Hs-CRP) POD risk. The total population consisted individuals a mean age 64.02 ± 13.20 years, 506 (78.60%) whom male, 114 (17.7%) had Compared lower group, in higher group exhibited age, heart rate, white blood cell count, urea nitrogen, creatinine, uric acid, fasting glucose, hemoglobin A1c, fibrinogen, D-dimer, prevalence CKD, but hemoglobin, high-density lipoprotein cholesterol, albumin estimated glomerular filtration rate. Additionally, (24.7% vs. 9.5%, p < 0.001). Multivariate confirmed that elevated its forms (Log10Hs-CRP, standardized Hs-CRP, group) consistently increased across all adjusted models (p 0.05). Stratified further highlighted significant associations specific subgroups, notably aged ≥65 female patients, those or without hypertension, diabetes, stroke history, chronic kidney disease ROC demonstrated ability overall (AUC = 0.646), as well male 0.644) 0.654). RCS indicated positive Log10Hs-CRP 0.003, nonlinear 0.896). Elevated are significantly associated an

Language: Английский

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Shared Mechanisms of Blood-Brain Barrier Dysfunction and Neuroinflammation in COVID-19 and Alzheimer’s Disease

American Journal Of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the virus's impact on central nervous system (CNS) and its potential to exacerbate neurodegenerative diseases like Alzheimer's disease (AD). Emerging evidence suggests that SARS-CoV-2 infection contributes chronic neuroinflammation, a key driver in etiopathogenesis of AD. Shared mechanisms, including blood-brain barrier (BBB) dysfunction, systemic inflammation, activation immune pathways, may link AD onset and/or progression, particularly among vulnerable individuals, such as those advanced age. This review explores convergent pathways involving renin-angiotensin-aldosterone (RAAS), Wnt/β-catenin signaling, NFκB activation, interferon (IFN) focusing their roles BBB integrity neuroinflammation. SARS-CoV-2-mediated ACE2 depletion disrupts RAAS homeostasis, favoring proinflammatory signaling parallels vascular dysfunction Dysregulation exacerbates permeability, while IFN contribute breakdown propagate CNS inflammation via endothelial cell activation. These interactions amplify prodromal pathology initiate pathogenesis. By identifying mechanistic overlaps between AD, this underscores need for therapeutic strategies targeting shared dysfunction. Understanding these connections is critical mitigating long-term neurological sequelae reducing burden

Language: Английский

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Neuroinflammation in Post COVID‐19 Sequelae: Neuroinvasion and Neuroimmune Crosstalk

Reviews in Medical Virology, Journal Year: 2024, Volume and Issue: 34(6)

Published: Nov. 1, 2024

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in December 2019 triggered a swift global spread, leading to devastating pandemic. Alarmingly, approximately one four individuals diagnosed with disease (COVID‐19) experience varying degrees cognitive impairment, raising concerns about potential increase neurological sequelae cases. Neuroinflammation seems be the key pathophysiological hallmark linking mild COVID‐19 fatigue, and patients, highlighting interaction between nervous immune systems following SARS‐CoV‐2 infection. Several hypotheses have been proposed explain how virus disrupts physiological pathways trigger inflammation within CNS, potentially neuronal damage. These include neuroinvasion, systemic inflammation, disruption lung gut‐brain axes, reactivation latent viruses. This review explores origins neuroinflammation underlying neuroimmune cross‐talk, important unanswered questions field. Addressing these fundamental issues could enhance our understanding virus's impact on CNS inform strategies mitigate its detrimental effects.

Language: Английский

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Oligodendrocyte Precursor Cell Transplantation Attenuates Inflammation after Ischemic Stroke in Mice

Published: Jan. 1, 2024

Language: Английский

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