Microglia at the blood brain barrier in health and disease

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Март 13, 2024

The blood brain barrier (BBB) plays a crucial role in maintaining homeostasis by selectively preventing the entry of substances from peripheral into central nervous system (CNS). Comprised endothelial cells, pericytes, and astrocytes, this highly regulated encompasses majority brain’s vasculature. In addition to its protective function, BBB also engages significant crosstalk with perivascular macrophages (MΦ) microglia, resident MΦ brain. These interactions play pivotal modulating activation state cells comprising BBB, as well MΦs themselves. Alterations systemic metabolic inflammatory states can promote cell dysfunction, reducing integrity potentially allowing factors leak CNS compartment. This may mediate MΦs, initiate further immune responses within parenchyma, suggesting neuroinflammation be triggered signaling periphery, without primary injury or disease originating CNS. intricate interplay between periphery through highlights importance understanding microglia mediating challenges. Despite recent advancements, our is still early stages, leaving gap knowledge. However, emerging research shedding light on involvement at various conditions, including infections, diabetes, ischemic stroke. review aims provide comprehensive overview current investigating relationship health disease. By exploring these connections, we hope advance challenges their impact pathology. Uncovering hold promise for development novel therapeutic strategies neurological conditions that involve vascular mechanisms.

Язык: Английский

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Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Abstract Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase infection, affecting approximately 10% to over 30% those infected. It presents a significant clinical challenge, notably due pronounced neurocognitive such brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing central role cerebromicrovascular dysfunction. This review investigates key pathophysiological contributing cerebrovascular dysfunction in long and their impacts on health. We discuss how endothelial tropism direct vascular trigger dysfunction, impaired neurovascular coupling, blood–brain barrier disruption, resulting compromised cerebral perfusion. Furthermore, appears induce mitochondrial enhancing oxidative stress inflammation within cells. Autoantibody formation following also potentially exacerbates injury, chronic ongoing compromise. These factors collectively contribute emergence white matter hyperintensities, promote amyloid pathology, may accelerate neurodegenerative processes, including Alzheimer’s disease. emphasizes critical advanced imaging techniques assessing health need for targeted interventions address complications. A deeper understanding essential advance treatments mitigate its long-term consequences.

Язык: Английский

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Virus-induced brain pathology and the neuroinflammation-inflammation continuum: the neurochemists view

Journal of Neural Transmission, Год журнала: 2024, Номер unknown

Опубликована: Янв. 23, 2024

Abstract Fascinatingly, an abundance of recent studies has subscribed to the importance cytotoxic immune mechanisms that appear increase risk/trigger for many progressive neurodegenerative disorders, including Parkinson’s disease (PD), Alzheimer’s (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with neuroinflammatory cascades, such as ageing, immunologic dysfunction, eventually disruption blood–brain barrier “cytokine storm”, be orchestrated mainly through activation microglial cells communication neurons. The inflammatory processes prompt cellular protein dyshomeostasis. share a common feature marked by characteristic pathological hallmarks abnormal neuronal accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or case AD, they are Aβ deposits tau-containing neurofibrillary tangles. Subsequently, these further elicit neurotoxic events which contribute onset neurodegeneration its progression aggravation neuroinflammation. However, there is caveat exclusively linking neuroinflammation neurodegeneration, since it’s highly unlikely dysregulation only factor contributes manifestation disorders. It unquestionably complex interaction other factors genetics, age, environment. This endorses “multiple hit hypothesis”. Consequently, if host genetic susceptibility coupled age-related weakened system, this makes them more susceptible virus/bacteria-related infection. may trigger chronic leading dyshomeostasis accumulation, finally, lead destruction. Here, we differentiate “neuroinflammation” “inflammation” regard involvement barrier, seems intact but defect inflammation. There neuroinflammation-inflammation continuum virus-induced brain affection. Therefore, propose staging process, might developed adding blood- CSF parameters, their stage-dependent composition severeness grade. If so, suitable optimise therapeutic strategies fight beginning avoid inflammation at all.

Язык: Английский

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Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas

Frontiers in Neurology, Год журнала: 2023, Номер 14

Опубликована: Июль 13, 2023

Introduction This study aimed to investigate microglial and macrophage activation in 17 patients who died the context of a COVID-19 infection 2020 2021. Methods Through immunohistochemical analysis, lysosomal marker CD68 was used detect diffuse parenchymal activity, pronounced perivascular clusters. were compared control grouped regarding clinical aspects. Detection viral proteins attempted different regions through multiple commercially available antibodies. Results Microglial most white matter with emphasis brain stem cerebellar areas. Analysis lesion patterns yielded no correlation between disease severity neuropathological changes. Occurrence clusters could not be associated severe course or preconditions but represent more advanced stage activation. Severe changes comparable Influenza. Hypoxic damage confounder described neuropathology. The macrophage/microglia reaction less post patients, detectable i.e. stem. Commercially antibodies for detection SARS-CoV-2 virus material immunohistochemistry specific signal over controls. Conclusion presented might an explanation long COVID syndrome.

Язык: Английский

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Clinical and immune evolution in neurological/psychiatric patients during the COVID-19 pandemic

Neurology Perspectives, Год журнала: 2025, Номер unknown, С. 100189 - 100189

Опубликована: Март 1, 2025

Язык: Английский

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Updates on the neurological manifestations of SARS-CoV-2 infection

Current Opinion in Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Purpose of review Since its emergence in 2020, the COVID-19 pandemic has created a global surge survivors experiencing neurologic effects from SARS-CoV-2 infection. This aims to provide an updated synthesis acute and chronic neurological manifestations COVID-19, outline current therapeutic strategies for these conditions. Recent findings Epidemiological studies have shown that patients with symptoms during infection tend poorer hospital functional outcomes. While risk adverse including cognitive dysfunction, headache, autonomic fatigue are thought be greatest following original strain alpha variant, they remain prevalent after subsequent less virulent strains as well. Some recent work also found link between structural brain changes. However, ongoing trials show promising results pharmacologic nonpharmacologic treatments targeting postacute sequelae COVID-19. Summary Lingering still pose considerable individual, healthcare system, socioeconomic repercussions. Both preventive multimodal treatment approaches necessary address Further research is required assess lasting impacts on nervous particularly potential contribution development neurodegenerative diseases.

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Апрель 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

Язык: Английский

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Phase Separation of SARS-CoV-2 Nucleocapsid Protein with TDP-43 Is Dependent on C-Terminus Domains

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8779 - 8779

Опубликована: Авг. 12, 2024

The SARS-CoV-2 nucleocapsid protein (N protein) is critical in viral replication by undergoing liquid-liquid phase separation to seed the formation of a ribonucleoprotein (RNP) complex drive genomic RNA (gRNA) translation and suppressing both stress granules processing bodies, which postulated increase uncoated gRNA availability. N can also form biomolecular condensates with broad range host endogenous proteins including binding (RBPs). Amongst these RBPs are that associated pathological, neuronal, glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, TAR DNA 43 kDa (TDP-43) forms pathological over 95% amyotrophic lateral sclerosis cases. In this study, we demonstrate TDP-43 dependent on C-terminus domain (N-CTD) intrinsically disordered TDP-43. This process markedly accelerated presence RNA. silico modeling suggests condensate composed an quadriplex C terminus incorporated.

Язык: Английский

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Role of the SARS-CoV-2 Virus in Brain Cells

Viral Immunology, Год журнала: 2024, Номер 37(2), С. 61 - 78

Опубликована: Фев. 5, 2024

COVID-19, caused by the SARS-CoV-2 virus, can have neurological effects, including cognitive symptoms like brain fog and memory problems. Research on effects of COVID-19 is ongoing, factors such as inflammation, disrupted blood flow, damage to vessels may contribute symptoms. Notably, some authors existing evidence suggest that virus enter central nervous system through different routes, olfactory nerve bloodstream. infection has been associated with altered consciousness, headaches, dizziness, mental disorders. The exact mechanisms impact formation shrinkage are still being studied. This review will focus pathways blood–brain barrier disruption, it then highlight interactions cell types in brain, namely neurons, astrocytes, oligodendrocytes, microglia.

Язык: Английский

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Unseen scars: Unraveling the neurological manifestations of COVID-19

Medicina Clínica, Год журнала: 2024, Номер 163(1), С. 21 - 24

Опубликована: Фев. 19, 2024

Язык: Английский

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