Blood-Brain Barrier: More Contributor to Disruption of Central Nervous System Homeostasis Than Victim in Neurological Disorders DOI Creative Commons

Minjia Xiao,

Zhi Jie Xiao,

Binbin Yang

et al.

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Aug. 6, 2020

The blood-brain barrier (BBB) is a dynamic but solid shield in the cerebral microvascular system. It plays pivotal role maintaining central nervous system (CNS) homeostasis by regulating exchange of materials between circulation and brain, protects neural tissue from neurotoxic components as well pathogens. Here, we discuss development BBB physiological conditions then focus on cerebrovascular disease, including acute ischemic stroke intracerebral hemorrhage, neurodegenerative disorders, such Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS). Finally, summarize recent advancements therapies targeting outline future directions outstanding questions field. We propose that dysfunction not only results causal pathogenesis neurological disorders; more contributor to disruption CNS than victim disorders.

Language: Английский

Glucose metabolic crosstalk and regulation in brain function and diseases DOI
Shuai Zhang, Brittany Bolduc Lachance, Mark P. Mattson

et al.

Progress in Neurobiology, Journal Year: 2021, Volume and Issue: 204, P. 102089 - 102089

Published: June 10, 2021

Language: Английский

Citations

116
Cerebral Edema Formation After Stroke: Emphasis on Blood–Brain Barrier and the Lymphatic Drainage System of the Brain DOI Creative Commons
Sichao Chen,

Linqian Shao,

Li Ma

et al.

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

Published: Aug. 16, 2021

Brain edema is a severe stroke complication that associated with prolonged hospitalization and poor outcomes. Swollen tissues in the brain compromise cerebral perfusion may also result transtentorial herniation. As physical biochemical barrier between peripheral circulation central nervous system (CNS), blood–brain (BBB) plays vital role maintaining stable microenvironment of CNS. Under pathological conditions, such as ischemic stroke, dysfunction BBB results increased paracellular permeability, directly contributing to extravasation blood components into causing vasogenic edema. Recent studies have led discovery glymphatic meningeal lymphatic vessels, which provide channel for cerebrospinal fluid (CSF) enter drain nearby lymph nodes communicate immune system, modulating surveillance responses. A deeper understanding function calls question known mechanisms after stroke. In this review, we first discuss how disruption can cause or contribute from perspective molecular cellular pathophysiology. Finally, participates formation summarize pathophysiological process two directions system.

Language: Английский

Citations

115
Mitochondria-containing extracellular vesicles (EV) reduce mouse brain infarct sizes and EV/HSP27 protect ischemic brain endothelial cultures DOI Creative Commons
Kandarp M. Dave, Donna B. Stolz, Venugopal Reddy Venna

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 354, P. 368 - 393

Published: Jan. 18, 2023

Language: Английский

Citations

51
Cellular and molecular mechanisms of the blood–brain barrier dysfunction in neurodegenerative diseases DOI Creative Commons

Tongli Chen,

Yan Dai,

Chenghao Hu

et al.

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

Published: July 19, 2024

Abstract Background Maintaining the structural and functional integrity of blood–brain barrier (BBB) is vital for neuronal equilibrium optimal brain function. Disruptions to BBB performance are implicated in pathology neurodegenerative diseases. Main body Early indicators multiple disorders humans animal models include impaired stability, regional cerebral blood flow shortfalls, vascular inflammation associated with dysfunction. Understanding cellular molecular mechanisms dysfunction crucial elucidating sustenance neural computations under pathological conditions developing treatments these This paper initially explores definition BBB, along signaling pathways regulating flow, inflammation. Subsequently, we review current insights into dynamics Alzheimer’s disease, Parkinson's amyotrophic lateral sclerosis, sclerosis. The concludes by proposing a unified mechanism whereby contributes disorders, highlights potential BBB-focused therapeutic strategies targets, outlines lessons learned future research directions. Conclusions breakdown significantly impacts development progression diseases, unraveling underlying elucidate how sustained devise approaches.

Language: Английский

Citations

31
Exposure to different surface-modified polystyrene nanoparticles caused anxiety, depression, and social deficit in mice via damaging mitochondria in neurons DOI
Yuhan Ma, Dihui Xu,

Zicheng Wan

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 919, P. 170739 - 170739

Published: Feb. 9, 2024

Language: Английский

Citations

23
Mitochondria in brain diseases: Bridging structural-mechanistic insights into precision-targeted therapies DOI Creative Commons
Jun Liao, Wenxiu He, Lisha Li

et al.

Published: Feb. 1, 2025

Language: Английский

Citations

3
Engineered mitochondria in diseases: mechanisms, strategies, and applications DOI Creative Commons
Mingyang Li, Limin Wu, Haibo Si

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 3, 2025

Abstract Mitochondrial diseases represent one of the most prevalent and debilitating categories hereditary disorders, characterized by significant genetic, biological, clinical heterogeneity, which has driven development field engineered mitochondria. With growing recognition pathogenic role damaged mitochondria in aging, oxidative inflammatory diseases, cancer, application expanded to those non-hereditary contexts (sometimes referred as mitochondria-related diseases). Due their unique non-eukaryotic origins endosymbiotic relationship, are considered highly suitable for gene editing intercellular transplantation, remarkable progress been achieved two promising therapeutic strategies—mitochondrial artificial mitochondrial transfer (collectively this review) over past decades. Here, we provide a comprehensive review mechanisms recent advancements applications, alongside concise summary potential implications supporting evidence from preclinical studies. Additionally, an emerging potentially feasible approach involves ex vivo editing, followed selection holds overcome limitations such reduced operability introduction allogeneic thereby broadening applicability

Language: Английский

Citations

2
Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke DOI Open Access

Masanori Naito,

Daichao Xu, Palak Amin

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(9), P. 4959 - 4970

Published: Feb. 18, 2020

Significance Necroptosis has been defined as a regulated cell death mechanism that can be activated under apoptosis deficient conditions. Here we show necroptosis brain ischemic conditions without inhibition of apoptosis. Furthermore, neuronal followed by delayed after the reduction TAK1 Our study demonstrates complex interaction and insult suggests therapeutic targeting RIPK1 kinase for treatment stroke.

Language: Английский

Citations

136
Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction DOI Creative Commons

Keqing Nian,

Ian C. Harding, Ira M. Herman

et al.

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 22, 2020

Ischemic stroke, a major cause of mortality in the United States, often contributes to disruption blood-brain barrier (BBB). The BBB along with its supportive cells, collectively referred as “neurovascular unit,” is brain’s multicellular microvasculature that bi-directionally regulates transport blood, ions, oxygen, and cells from circulation into brain. It thus vital for maintenance central nervous system homeostasis. disruption, which associated altered expression tight junction proteins transporters, believed exacerbate brain injury caused by ischemic stroke limits therapeutic potential current clinical therapies, such recombinant tissue plasminogen activator. Accumulating evidence suggests endothelial mechanobiology, conversion mechanical forces biochemical signals, helps regulate function peripheral vasculature may similarly maintain integrity. For example, glycocalyx (GCX), glycoprotein-proteoglycan layer extending lumen bloods vessel, abundantly expressed on has been shown permeability. In this review, we will focus our understanding mechanisms underlying damage after highlighting future novel pharmacological strategies protection recovery. Finally, address knowledge mechanotransduction maintenance, specifically focusing role GCX.

Language: Английский

Citations

125
In vitro modeling of the neurovascular unit: advances in the field DOI Creative Commons
Aditya Bhalerao, Farzane Sivandzade, Sabrina Rahman Archie

et al.

Fluids and Barriers of the CNS, Journal Year: 2020, Volume and Issue: 17(1)

Published: March 16, 2020

Abstract The blood–brain barrier (BBB) is a fundamental component of the central nervous system. Its functional and structural integrity vital in maintaining homeostasis brain microenvironment. On other hand, BBB also major hindering obstacle for delivery effective therapies to treat disorders Central Nervous System (CNS). Over time, various model systems have been established simulate complexities BBB. development realistic vitro models that accurately mimic physiological characteristics microcapillaries situ importance not only CNS drug discovery but translational research. Successful modeling Neurovascular Unit (NVU) would provide an invaluable tool aid dissecting out pathological factors, mechanisms action, corresponding targets prodromal onset disorders. field has seen many changes last few years with introduction novel tools methods improve existing enable new ones. organoids, organ-on-chip, spheroids, 3D printed microfluidics, innovative technologies potential advance NVU modeling. Therefore, this review, summarize advances progress design application platforms focus on rapidly advancing technologies.

Language: Английский

Citations

122