Circadian rhythms in the blood–brain barrier: impact on neurological disorders and stress responses DOI Creative Commons
Nicolette Schurhoff, Michał Toborek

Molecular Brain, Journal Year: 2023, Volume and Issue: 16(1)

Published: Jan. 12, 2023

Circadian disruption has become more prevalent in society due to the increase shift work, sleep disruption, blue light exposure, and travel via different time zones. The circadian rhythm is a timed transcription-translation feedback loop with positive regulators, BMAL1 CLOCK, that interact negative CRY PER, regulate both central peripheral clocks. This review highlights functions of rhythm, specifically blood-brain barrier (BBB), during healthy pathological states. BBB highly selective dynamic interface composed CNS endothelial cells, astrocytes, pericytes, neurons, microglia form neurovascular unit (NVU). rhythms modulate integrity through regulating oscillations tight junction proteins, assisting NVU, modulating transporter functions. disruptions within have been observed stress responses several neurological disorders, including brain metastasis, epilepsy, Alzheimer's disease, Parkinson's disease. Further understanding these interactions may facilitate development improved treatment options preventative measures.

Language: Английский

Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation DOI
Jurgen A.H.R. Claassen, Dick H. J. Thijssen, Ronney B. Panerai

et al.

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(4), P. 1487 - 1559

Published: March 26, 2021

Brain function critically depends on a close matching between metabolic demands, appropriate delivery of oxygen and nutrients, removal cellular waste. This requires continuous regulation cerebral blood flow (CBF), which can be categorized into four broad topics:

Language: Английский

Citations

549
Revisiting the neurovascular unit DOI

Samantha Schaeffer,

Costantino Iadecola

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(9), P. 1198 - 1209

Published: Aug. 5, 2021

Language: Английский

Citations

430
The blood-brain barrier in aging and neurodegeneration DOI Creative Commons
Emily G. Knox, María R. Aburto, Gerard Clarke

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(6), P. 2659 - 2673

Published: March 31, 2022

Abstract The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange compounds between the blood and parenchyma. Moreover, BBB prevents unwanted toxins pathogens from entering brain. This barrier, however, breaks down with age further disruption a hallmark many age-related disorders. Several drugs have been explored, thus far, to protect or restore function. With recent connection gut microbiota, microbial-derived metabolites explored their capabilities physiology. review, will focus on components that make up BBB, dissect levels discuss current therapeutics maintain integrity discoveries effects

Language: Английский

Citations

371
Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies DOI Creative Commons
Kevin R. Parker, Denis Migliorini, Eric Perkey

et al.

Cell, Journal Year: 2020, Volume and Issue: 183(1), P. 126 - 142.e17

Published: Sept. 21, 2020

Language: Английский

Citations

357
Blood–Brain Barrier Breakdown: An Emerging Biomarker of Cognitive Impairment in Normal Aging and Dementia DOI Creative Commons
Basharat Hussain, Cheng Fang, Junlei Chang

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Aug. 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.

Language: Английский

Citations

186
Pericyte Control of Blood Flow Across Microvascular Zones in the Central Nervous System DOI
David A. Hartmann, Vanessa Coelho‐Santos, Andy Y. Shih

et al.

Annual Review of Physiology, Journal Year: 2021, Volume and Issue: 84(1), P. 331 - 354

Published: Oct. 21, 2021

The vast majority of the brain's vascular length is composed capillaries, where our understanding blood flow control remains incomplete. This review synthesizes current knowledge on across microvascular zones by addressing issues with nomenclature and drawing new developments from in vivo optical imaging single-cell transcriptomics. Recent studies have highlighted important distinctions mural cell morphology, gene expression, contractile dynamics, which can explain observed differences response to vasoactive mediators between arteriole, transitional, capillary zones. Smooth muscle cells arterioles ensheathing pericytes arteriole-capillary transitional zone large-scale, rapid changes flow. In contrast, downstream act slower smaller scales are involved establishing resting tone heterogeneity. Many unresolved remain, including that activate different pericyte types vivo, role pericyte-endothelial communication conducting signals capillaries arterioles, how neurological disease affects these mechanisms.

Language: Английский

Citations

135
Factors influencing the blood-brain barrier permeability DOI Creative Commons
Yibin Zhao, Lin Gan, Li Ren

et al.

Brain Research, Journal Year: 2022, Volume and Issue: 1788, P. 147937 - 147937

Published: May 11, 2022

The blood-brain barrier (BBB) is a dynamic structure that protects the brain from harmful blood-borne, endogenous and exogenous substances maintains homeostatic microenvironment. All constituent cell types play indispensable roles in BBB's integrity, other structural BBB components, such as tight junction proteins, adherens junctions, junctional can control permeability. Regarding need to exchange nutrients toxic materials, solute carriers, ATP-binding case families, ion transporter, well transcytosis regulate influx efflux transport, while difference localisation expression contribute functional differences transport properties. Numerous chemical mediators factors non-physicochemical have been identified alter permeability by mediating components function, because of close relationship with inflammation. In this review, we highlight recently gained mechanistic insights into maintenance disruption BBB. A better understanding influencing could supporting promising potential therapeutic targets for protecting delivery central nervous system drugs via interventions under pathological conditions.

Language: Английский

Citations

126
Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease DOI Creative Commons
Yasuteru Inoue, Francis Shue, Guojun Bu

et al.

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: July 11, 2023

Abstract Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large small vessels a key driver of age-related decline. Severe VCID includes post-stroke dementia, subcortical ischemic multi-infarct mixed dementia. While acknowledged as the second most common form after Alzheimer’s disease (AD) accounting for 20% cases, AD frequently coexist. In VCID, vessel (cSVD) often affects arterioles, capillaries, venules, where arteriolosclerosis amyloid angiopathy (CAA) are major pathologies. White matter hyperintensities, recent infarcts, lacunes presumed origin, enlarged perivascular space, microbleeds, brain atrophy neuroimaging hallmarks cSVD. The current primary approach to cSVD treatment control risk factors such hypertension, dyslipidemia, diabetes, smoking. However, causal therapeutic strategies have not been established partly due heterogeneous pathogenesis this review, we summarize pathophysiology discuss probable etiological pathways focusing on hypoperfusion/hypoxia, blood–brain barriers (BBB) dysregulation, fluid drainage disturbances, inflammation define potential diagnostic targets

Language: Английский

Citations

110
Formononetin protects against inflammation associated with cerebral ischemia-reperfusion injury in rats by targeting the JAK2/STAT3 signaling pathway DOI Open Access
Li Yu, Yangyang Zhang, Qianqian Chen

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 149, P. 112836 - 112836

Published: March 24, 2022

Formononetin is a type of phytoestrogen obtained from the Chinese medical herb Red Clover. It exhibits anti-neoplastic hepatoprotective, and neuroprotective properties. However, anti-inflammatory effect formononetin in cerebral ischemia-reperfusion injury has not been reported. To explore potential mechanism action with regard to JAK2/STAT3 signaling pathway. Male SD rats were used establish middle artery occlusion (MCAO) model randomly divided into 5 groups: Sham, MCAO, JAK2 Inhibitor (Ag490), Formononetin, + Formononetin. The protective MCAO was detected by performing neurological deficit testing, TTC staining, H&E Nissl ELISA, RT-PCR, western blotting immunofluorescence. significantly alleviated pathological state brain tissues, reduced volume infarction, levels IL-18 TNF-α inflammatory factors plasma, mRNA IL-6 IL-1β rat tissue, protein p-JAK2, p-STAT3, NLRP3, ASC, cl-Caspase-1, cl-IL-1β tissue. effects. may inhibit relevant targets pathway, thereby having certain against injury.

Language: Английский

Citations

99
Endothelial Dysfunction in Neurodegenerative Diseases DOI Open Access

Yao‐Ching Fang,

Yi‐Chen Hsieh, Chaur‐Jong Hu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2909 - 2909

Published: Feb. 2, 2023

The cerebral vascular system stringently regulates blood flow (CBF). components of the blood–brain barrier (BBB) protect brain from pathogenic infections and harmful substances, efflux waste, exchange substances; however, diseases develop in cases vessel injuries BBB dysregulation. Vascular pathology is concurrent with mechanisms underlying aging, Alzheimer’s disease (AD), dementia (VaD), which suggests its involvement these mechanisms. Therefore, present study, we reviewed role dysfunction aging neurodegenerative diseases, particularly AD VaD. During development aforementioned changes occur morphology local cells, which, turn, alter CBF, fluid dynamics, integrity. Chronic inflammation dysregulation further exacerbate dysfunction. Multitudinous processes affect cerebrovascular system, whose causes cognitive impairment. Knowledge regarding pathophysiology molecular may lead to discovery clinically relevant biomarkers, facilitate imaging for prevention treatment.

Language: Английский

Citations

46