The role of the blood–brain barrier during neurological disease and infection

Biochemical Society Transactions, Год журнала: 2023, Номер 51(2), С. 613 - 626

Опубликована: Март 17, 2023

A healthy brain is protected by the blood–brain barrier (BBB), which formed endothelial cells that line capillaries. The BBB plays an extremely important role in supporting normal neuronal function maintaining homeostasis of microenvironment and restricting pathogen toxin entry to brain. Dysfunction this highly complex regulated structure can be life threatening. dysfunction implicated many neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, infections. Among other mechanisms, inflammation and/or flow disturbances are major causes infections diseases. In particular, ischaemic both contribute disruption, leading devastating consequences. While a transient or minor disruption could tolerated, chronic total breach result irreversible damage. It worth noting timing extent play process any repair damage treatment strategies. This review evaluates summarises some latest research on during disease infection with focus effects BBB. BBB's crucial protecting also bottleneck central nervous system drug development. Therefore, innovative strategies carry therapeutics across novel models screen drugs, study complex, overlapping mechanisms urgently needed.

Язык: Английский

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Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10458 - 10458

Опубликована: Июнь 21, 2023

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low-grade inflammatory response; immune dysregulation defective reactivation latent viruses; autoimmunity; persistent endothelial dysfunction coagulopathy; gut dysbiosis; hormonal metabolic dysregulation; mitochondrial dysfunction; autonomic nervous system dysfunction. There are no specific tests for diagnosis LC, clinical features laboratory findings biomarkers not specifically relate to LC. Therefore, is paramount importance develop validate that can employed prediction, prognosis its therapeutic response, although this effort hampered challenges pertaining non-specific nature majority manifestations in spectrum, small sample sizes relevant studies other methodological issues. Promising candidate found some patients markers systemic inflammation, acute phase proteins, cytokines chemokines; reflecting persistence, herpesviruses endotheliopathy, coagulation fibrinolysis; microbiota alterations; diverse proteins metabolites; biomarkers; cerebrospinal fluid biomarkers. At present, there only two reviews summarizing they do cover entire umbrella current biomarkers, their link etiopathogenetic mechanisms or diagnostic work-up comprehensive manner. Herein, we aim appraise synopsize available evidence on typical classification based pathogenetic main symptomatology frame epidemiological aspects syndrome furthermore assess limitations as well potential implications interventions.

Язык: Английский

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Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients

The Journal of Infectious Diseases, Год журнала: 2020, Номер 223(4), С. 600 - 609

Опубликована: Ноя. 26, 2020

Abstract Background Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings. Methods The study included COVID-19 whom severe acute respiratory syndrome 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening on CSF were performed. Clinical, laboratory, brain magnetic resonance (MR) imaging data retrospectively collected analyzed. Results Patients mostly men (66%), a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), headaches (5%). protein albumin levels increased 38% 23%, respectively. A total 40% displayed an elevated quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band found 5 (11%), intrathecal synthesis G, 26 (55%) presented identical bands serum CSF. Four (7%) had positive SARS-CoV-2 reaction. Leptomeningeal enhancement present MR images 20 (38%). Conclusions Brain abnormalities, especially leptomeningeal enhancement, inflammatory markers related to COVID-19, whereas detection remained scanty.

Язык: Английский

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Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Июль 29, 2021

Abstract Background Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 infect brains. While mechanisms this process not fully understood, it has been proposed that can cells neurovascular unit (NVU), which form blood-brain barrier (BBB). The aim current study was analyze expression pattern main receptors naïve and HIV-1-infected NVU order elucidate a possible pathway virus entry into brain potential modulatory impact HIV-1 process. Methods gene protein profile ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B, L assessed qPCR, immunoblotting, immunostaining, respectively. In addition, we investigated if endothelial be exposure S1 subunit S protein, domain responsible for direct binding ACE2 receptors. Results involved infection co-expressed NVU, especially astrocytes microglial cells. These functionally active as SARS CoV-2 altered tight junction proteins, such claudin-5 ZO-1. Additionally, upregulated TMPRSS2 microglia Conclusions findings provide key insight recognition may help develop treatment CNS COVID-19.

Язык: Английский

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Rehabilitation and COVID-19: the Cochrane Rehabilitation 2020 rapid living systematic review. Update as of July 31st, 2020

European Journal of Physical and Rehabilitation Medicine, Год журнала: 2020, Номер 56(5)

Опубликована: Ноя. 1, 2020

INTRODUCTION: This paper is the first update of second edition rapid living systematic review on latest scientific literature informing rehabilitation patients with COVID-19 and/or describing consequences disease and its treatment, as they relate to limitations in functioning interest. The aim this study was report data a search performed papers published July 2020.EVIDENCE ACQUISITION: methodology described applied eligible included databases between 1, 2020 31, SYNTHESIS: Eight-hundred-ninety-two were identified through database searching (after removal duplicates); these, only 23 studies included. According OCEBM 2011 Levels Evidence Table, level 3 30.5% cases 4 69.5%. No RCT found. Nineteen studied patients, assessed acute (10 studies), post-acute (8 studies) chronic phase (one study). Four reported impact subjects pre-existing health conditions.CONCLUSIONS: current production still focuses more all possible aspects complications pathology than interventions or new organization models deal it. Albeit evidence handling from rehabilitative point view improving each month, further are mandatory role scenario.

Язык: Английский

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