ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Delayed inhibition of VEGF signaling after stroke attenuates blood-brain barrier breakdown and improves functional recovery in a comorbidity-dependent manner.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 136 citations in OpenAlex.
- Short-chain fatty acids as key mediators of the microbiota-gut-brain axis in chronic cerebral hypoperfusion: mechanisms and therapeutics.Molecular medicine (Cambridge, Mass.) · 2026Review
- Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption.Cell death & disease · 2026Article
- Injectable micropore-forming microgel scaffold for neural progenitor cells transplantation and vascularization after stroke.Nature communications · 2025Article
- Prognostic Significance of Plasma VEGFA and VEGFR2 in Acute Ischemic Stroke-a Prospective Cohort Study.Molecular neurobiology · 2024Article
- Exosomes Interactions with the Blood-Brain Barrier: Implications for Cerebral Disorders and Therapeutics.International journal of molecular sciences · 2023Review
- Mild Traumatic Brain Injury Induces Time- and Sex-Dependent Cerebrovascular Dysfunction and Stroke Vulnerability.Journal of neurotrauma · 2023Article
- The age-dependent immune response to ischemic stroke.Current opinion in neurobiology · 2023Review
- Association between vascular endothelial growth factor-mediated blood-brain barrier dysfunction and stress-induced depression.Molecular psychiatry · 2022Article
- VEGF, a Key Factor for Blood Brain Barrier Injury After Cerebral Ischemic Stroke.Aging and disease · 2022Article
- Optimising the photothrombotic model of stroke in the C57BI/6 and FVB/N strains of mouse.Scientific reports · 2022Article
- Syndecan-2 selectively regulates VEGF-induced vascular permeability.Nature cardiovascular research · 2022Article
- Analysis of Research Directions on the Rehabilitation of Patients with Stroke and Diabetes Using Scientometric Methods.Healthcare (Basel, Switzerland) · 2022Review
- Vascular Sema3E-Plexin-D1 Signaling Reactivation Promotes Post-stroke Recovery through VEGF Downregulation in Mice.Translational stroke research · 2022Article
- Glycocalyx is critical for blood-brain barrier integrity by suppressing caveolin1-dependent endothelial transcytosis following ischemic stroke.Brain pathology (Zurich, Switzerland) · 2022Article
- The consequence of endothelial remodelling on the blood spinal cord barrier and nociception.Current research in physiology · 2022Review
- Healthy Serum-Derived Exosomes Improve Neurological Outcomes and Protect Blood-Brain Barrier by Inhibiting Endothelial Cell Apoptosis and Reversing Autophagy-Mediated Tight Junction Protein Reduction in Rat Stroke Model.Frontiers in cellular neuroscience · 2022Article
- Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome.Angiogenesis · 2021Article
- Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview.Pharmaceutics · 2021Review
- Longitudinal functional imaging of VIP interneurons reveals sup-population specific effects of stroke that are rescued with chemogenetic therapy.Nature communications · 2021Article
- Microvascular changes associated with epilepsy: A narrative review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Diabetes is a common comorbidity in stroke patients and a strong predictor of poor functional outcome. To provide a more mechanistic understanding of this clinically relevant problem, we focused on how diabetes affects blood-brain barrier (BBB) function after stroke. Because the BBB can be compromised for days after stroke and thus further exacerbate ischemic injury, manipulating its function presents a unique opportunity for enhancing stroke recovery long after the window for thrombolytics has passed. Using a mouse model of Type 1 diabetes, we discovered that ischemic stroke leads to an abnormal and persistent increase in vascular endothelial growth factor receptor 2 (VEGF-R2) expression in peri-infarct vascular networks. Correlating with this, BBB permeability was markedly increased in diabetic mice, which could not be prevented with insulin treatment after stroke. Imaging of capillary ultrastructure revealed that BBB permeability was associated with an increase in endothelial transcytosis rather than a loss of tight junctions. Pharmacological inhibition (initiated 2.5 d after stroke) or vascular-specific knockdown of VEGF-R2 after stroke attenuated BBB permeability, loss of synaptic structure in peri-infarct regions, and improved recovery of forepaw function. However, the beneficial effects of VEGF-R2 inhibition on stroke recovery were restricted to diabetic mice and appeared to worsen BBB permeability in nondiabetic mice. Collectively, these results suggest that aberrant VEGF signaling and BBB dysfunction after stroke plays a crucial role in limiting functional recovery in an experimental model of diabetes. Furthermore, our data highlight the need to develop more personalized stroke treatments for a heterogeneous clinical population.
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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.