ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2017
Mice deficient in endothelial α5 integrin are profoundly resistant to experimental ischemic stroke.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 53 citations in OpenAlex.
- A central role for fibrinogen in promoting microglial repair of the hypoxia-disrupted blood-brain barrier.Journal of neuroinflammation · 2026Article
- Endothelial αvβ3 integrin induction during hypoxia protects blood-brain barrier integrity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Partial eNOS Deficiency Results in Greater Levels of Vascular Inflammation and BBB Disruption in Response to Chronic Mild Hypoxia.International journal of molecular sciences · 2025Article
- Blood-brain barrier disruption and microglial activation during hypoxia and post-hypoxic recovery in aged mice.Brain communications · 2025Article
- MMP-3 Knockout Induces Global Transcriptional Changes and Reduces Cerebral Infarction in Both Male and Female Models of Ischemic Stroke.International journal of molecular sciences · 2024Article
- Cerebral arterioles express the laminin subunits α4 and α5 in conjunction with α6β4 integrin, but strongly downregulate laminin α4 during hypoxia-induced arteriogenic remodeling.Microvascular research · 2024Article
- Natural Fatty Acid Guards against Brain Endothelial Cell Death and Microvascular Pathology following Ischemic Insult in the Presence of Acute Hyperglycemia.Biomedicines · 2023Article
- The importance of laminin at the blood-brain barrier.Neural regeneration research · 2023Review
- β1 integrin is essential for blood-brain barrier integrity under stable and vascular remodelling conditions; effects differ with age.Fluids and barriers of the CNS · 2023Article
- Emerging Targets for Modulation of Immune Response and Inflammation in Stroke.Neurochemical research · 2023Review
- Cell-specific expression and function of laminin at the neurovascular unit.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Review
- Exaggerated hypoxic vascular breakdown in aged brain due to reduced microglial vasculo-protection.Aging cell · 2022Article
- The impact of genetic manipulation of laminin and integrins at the blood-brain barrier.Fluids and barriers of the CNS · 2022Review
- Article
- Modulation of gene expression on a transcriptome-wide level following human neural stem cell transplantation in aged mouse stroke brains.Experimental neurology · 2022Article
- Silencing of lncRNA XIST impairs angiogenesis and exacerbates cerebral vascular injury after ischemic stroke.Molecular therapy. Nucleic acids · 2021Article
- Article
- SARS-CoV-2 mediated neuroinflammation and the impact of COVID-19 in neurological disorders.Cytokine & growth factor reviews · 2021Review
- Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model.Journal of neuroendocrinology · 2021Article
- Mild hypoxia triggers transient blood-brain barrier disruption: a fundamental protective role for microglia.Acta neuropathologica communications · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2-3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no differences in cerebrovascular anatomy or collateral blood flow were noted that could account for this difference in ischemic injury. Rather, we demonstrate that α5 KOs have increased blood-brain barrier integrity (increased expression of claudin-5, and absent brain parenchymal IgG extravasation) after stroke compared with controls, which could explain their resistance to ischemic injury. Additionally, inhibition of α5 integrin in vitro leads to decreased permeability of brain endothelial cells following oxygen-glucose deprivation. Together, these findings indicate endothelial cell α5 integrin plays an important role in stroke outcome and blood-brain barrier integrity, suggesting that α5 integrin could be a novel therapeutic target for stroke.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.