Focusing on claudin-5: A promising candidate in the regulation of BBB to treat ischemic stroke

Lv, Jianjun; Hu, Wei; Yang, Zhi; Li, Tian; Jiang, Shuai; Ma, Zhiqiang; Chen, Fulin; Yang, Yang

doi:10.1016/j.pneurobio.2017.12.001

Cited by 148Barrier Structure and Function StudiesAcute Ischemic Stroke ManagementNeurological Disorders and Treatments

Focusing on claudin-5: A promising candidate in the regulation of BBB to treat ischemic stroke

Lv, Jianjun, Hu, Wei, Yang, Zhi, Li, Tian, Jiang, Shuai, Ma, Zhiqiang, Chen, Fulin, Yang, Yang·2018·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2017.12.001

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Abstract

Claudin-5 is a tight junction (TJ) protein in the blood-brain barrier (BBB) that has recently attracted increased attention. Numerous studies have demonstrated that claudin-5 regulates the integrity and permeability of the BBB. Increased claudin-5 expression plays a neuroprotective role in neurological diseases, particularly in cerebral ischemic stroke. Moreover, claudin-5 might be a potential marker for early hemorrhagic transformation detection in ischemic stroke. In light of the distinctive effects of claudin-5 on the nervous system, we present the elaborate network of roles that claudin-5 plays in ischemic stroke. In this review, we first introduce basic knowledge regarding the BBB and the claudin family, the characterization and regulation of claudin-5, and association between claudin-5 and other TJ proteins. Subsequently, we describe BBB dysfunction and neuron-specific drivers of pathogenesis of ischemic stroke, including inflammatory disequilibrium and oxidative stress. Furthermore, we summarize promising ischemic stroke treatments that target the BBB via claudin-5, including modified rt-PA therapy, pharmacotherapy, hormone treatment, receptor-targeted therapy, gene therapy, and physical therapy. This review highlights recent advances and provides a comprehensive summary of claudin-5 in the regulation of the BBB and may be helpful for drug design and clinical therapy for treatment of ischemic stroke.

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Astrocytic processes surround most of the vascular surface and regulate blood-brain barrier permeability by modulating tight junction proteins such as claudin-5 and endothelial proteins such as vimentin.
“Astrocytic processes surround most of the vascular surface, regulating the blood–brain barrier (BBB) permeability [6, 7, 8, 9]—by modulating tight junction proteins such as claudin‐5 [10], or endothelial proteins such vimentin, which is associated with the stability of cerebral vasculature [11]—and integrate neuronal activity with blood flow [1, 2, 3, 4, 5, 12, 13, 14, 15, 16, 17, 18, 19, 20].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp>APOE3</scp> Christchurch homozygote glioprotection (2023) · cites this paper as [10]
Claudin-5 is crucial for the selective permeability of the blood-brain barrier (BBB).
“claudin‐5 is crucial for the selective permeability of the BBB [10]”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp>APOE3</scp> Christchurch homozygote glioprotection (2023) · cites this paper as [10]

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Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?
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Theta-burst transcranial magnetic stimulation promotes stroke recovery by vascular protection and neovascularization
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Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis
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Endothelial Targets in Stroke
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Research progress of mechanisms for tight junction damage on blood–brain barrier inflammation
Zhao, B., Yin, Q., Fei, Y., Zhu, J., Qiu, Y.-Y., Fang, W., & Li, Y. (2020) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2020.1784952 · Cited by 65 · see citing works
Endothelium-targeted deletion of the miR-15a/16-1 cluster ameliorates blood-brain barrier dysfunction in ischemic stroke
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Sirt3 Protects Against Ischemic Stroke Injury by Regulating HIF-1α/VEGF Signaling and Blood–Brain Barrier Integrity
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Lithium alleviates blood-brain barrier breakdown after cerebral ischemia and reperfusion by upregulating endothelial Wnt/β-catenin signaling in mice
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Increase of blood-brain barrier leakage is related to cognitive decline in vascular mild cognitive impairment
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A novel PGAM5 inhibitor LFHP-1c protects blood–brain barrier integrity in ischemic stroke
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Profiling of Blood-Brain Barrier Disruption in Mouse Intracerebral Hemorrhage Models: Collagenase Injection vs. Autologous Arterial Whole Blood Infusion
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The Blood–Brain Barrier—A Key Player in Multiple Sclerosis Disease Mechanisms
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Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke
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Geniposide protects against hypoxia/reperfusion-induced blood-brain barrier impairment by increasing tight junction protein expression and decreasing inflammation, oxidative stress, and apoptosis in an in vitro system
Li, C., Wang, X., Cheng, F., Du, X., Yan, J., Zhai, C., Mu, J., & Wang, Q. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.04.021 · Cited by 55 · see citing works
Research developments in the neurovascular unit and the blood‑brain barrier (Review)
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Role of immune responses for extracellular matrix remodeling in the ischemic brain
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miR-27a-3p regulates expression of intercellular junctions at the brain endothelium and controls the endothelial barrier permeability
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1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea Protects the Blood-Brain Barrier Against Ischemic Injury by Upregulating Tight Junction Protein Expression, Mitigating Apoptosis and Inflammation InVivo and In Vitro Model
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Therapeutic Target and Cell-signal Communication of Chlorpromazine and Promethazine in Attenuating Blood–Brain Barrier Disruption after Ischemic Stroke
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Breakthrough of ZrO2 nanoparticles into fetal brains depends on developmental stage of maternal placental barrier and fetal blood-brain-barrier
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Effects of lipocalin-2 on brain endothelial adhesion and permeability
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Ferroptosis of brain microvascular endothelial cells contributes to hypoxia‐induced blood–brain barrier injury
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MicroRNA‐182 exacerbates blood‐brain barrier (BBB) disruption by downregulating the mTOR/FOXO1 pathway in cerebral ischemia
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Angioneurins – Key regulators of blood–brain barrier integrity during hypoxic and ischemic brain injury
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Expression of VEGF- and tight junction-related proteins in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy
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Extracellular Vesicles From 3xTg-AD Mouse and Alzheimer’s Disease Patient Astrocytes Impair Neuroglial and Vascular Components
González-Molina, L. A., Villar-Vesga, J., Henao-Restrepo, J., Villegas, A., Lopera, F., Cardona-Gómez, G. P., & Posada-Duque, R. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.593927 · Cited by 37 · see citing works
Inhibition of Transient Receptor Potential Vanilloid 1 Attenuates Blood–Brain Barrier Disruption after Traumatic Brain Injury in Mice
Yang, D., Yao, J., Liu, Y., Xu, Z., Yuan, F., Wang, M.-L., Geng, Z., & Tian, H. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5942 · Cited by 36 · see citing works
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Baicalin Reduces Immune Cell Infiltration by Inhibiting Inflammation and Protecting Tight Junctions in Ischemic Stroke Injury
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Anfibatide Preserves Blood–Brain Barrier Integrity by Inhibiting TLR4/RhoA/ROCK Pathway After Cerebral Ischemia/Reperfusion Injury in Rat
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Omentin-1: Protective impact on ischemic stroke via ameliorating atherosclerosis
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Disrupted Blood‐Brain Barrier and Mitochondrial Impairment by Autotaxin–Lysophosphatidic Acid Axis in Postischemic Stroke
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Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy
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Adiponectin accumulation in the retinal vascular endothelium and its possible role in preventing early diabetic microvascular damage
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Beyond the Walls of Troy: A Scoping Review on Pharmacological Strategies to Enhance Drug Delivery Across the Blood–Brain Barrier and Blood–Tumor Barrier
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HDAC 3 inhibition prevents oxygen glucose deprivation/reoxygenation‐induced transendothelial permeability by elevating PPAR γ activity in vitro
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Resveratrol Delivery by Albumin Nanoparticles Improved Neurological Function and Neuronal Damage in Transient Middle Cerebral Artery Occlusion Rats
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Beyond wrecking a wall: revisiting the concept of blood–brain barrier breakdown in ischemic stroke
Castillo-González, J., & González‐Rey, E. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00392 · Cited by 28 · see citing works
Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation
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XingNaoJing injections protect against cerebral ischemia/reperfusion injury and alleviate blood-brain barrier disruption in rats, through an underlying mechanism of NLRP3 inflammasomes suppression
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Shengui Sansheng Pulvis maintains blood-brain barrier integrity by vasoactive intestinal peptide after ischemic stroke
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Oral intake of ZrO2 nanoparticles by pregnant mice results in nanoparticles’ deposition in fetal brains
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Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels
Markov, A. G., Fedorova, A. A., Васильевна, К. В., Bikmurzina, A. E., Okorokova, L. S., Matchkov, V. V., Cornelius, V., Amasheh, S., & Krivoi, I. I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21145067 · Cited by 25 · see citing works
JLX001 attenuates blood-brain barrier dysfunction in MCAO/R rats via activating the Wnt/β-catenin signaling pathway
Zhao, B., Zhu, J., Fei, Y., Yin, Q., Shen, W., Liang, B., Zhu, X., & Li, Y. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118221 · Cited by 25 · see citing works
The role of microRNAs involved in the disorder of blood–brain barrier in the pathogenesis of multiple sclerosis
Nejad, A. E., Zadeh, S. M. M., Nickho, H., Abbasian, A. S., Forouzan, A., Ahmadlou, M., Nedaeinia, R., Shaverdi, S., & Manian, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1281567 · Cited by 26 · see citing works
Significance and Mechanisms of P-glycoprotein in Central Nervous System Diseases
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Authors: Lv, J., Hu, W., Yang, Z., Li, T., Jiang, S., Ma, Z., Chen, F., & Yang, Y.
Affiliations: Northwest University (CN)
Air Force Medical University (CN)
Tang Du Hospital (CN)
Corresponding author: Yang, Yang
ORCID: Lv, Jianjun
Hu, Wei
Yang, Zhi
Li, Tian
Jiang, Shuai
Ma, Zhiqiang
Chen, Fulin
Yang, Yang
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2018-02
Volume: 161
Pages: 79-96
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2017.12.001
OpenAlex: W2771763619
Cited by: 148
References: 179
Citations by year: 2026: 7 · 2025: 17 · 2024: 16 · 2023: 13 · 2022: 17 · 2021: 26 · 2020: 23 · 2019: 16 · 2018: 13
FWCI: 1.37
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81500263)
China Postdoctoral Science Foundation (2016T90973, 2015M572681)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords: claudin-5, blood-brain barrier, ischemic stroke, tight junction proteins, blood-brain barrier permeability, hemorrhagic transformation, neuroprotection, oxidative stress, neuroinflammation, gene therapy, hormone therapy, receptor-targeted therapy, physiotherapy
MeSH terms: Animals, Blood-Brain Barrier, Brain Ischemia, Humans, Tissue Plasminogen Activator, Tight Junctions, Stroke, Claudin-5

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Focusing on claudin-5: A promising candidate in the regulation of BBB to treat ischemic stroke

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