ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Exendin-4-loaded PLGA microspheres relieve cerebral ischemia/reperfusion injury and neurologic deficits through long-lasting bioactivity-mediated phosphorylated Akt/eNOS signaling in rats.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- The Pleiotropic Therapeutic Perspectives of GLP-1 and GIP Receptor Agonists in Spinal Cord Injury: A Narrative Review.Molecular neurobiology · 2026Review
- GLP-1 receptor agonists as multisystem therapies: from glycemic control to cardiorenal, neuroimmune, and metabolic disease.Diabetology & metabolic syndrome · 2026Review
- GLP-1 Receptor Agonists in Acute Ischemic Stroke and Secondary Stroke Prevention: A Narrative Review of Preclinical and Clinical Evidence.Journal of central nervous system disease · 2026Review
- Exosomal miR-450b-5p Secreted from Exendin-4-Stimulated Endothelial Cells Protects Retinal Ganglion Cells Against Ischemia Reperfusion Injury.International journal of nanomedicine · 2025Article
- RETRACTED: Chung et al. Long-Lasting Exendin-4-Loaded PLGA Nanoparticles Ameliorate Cerebral Ischemia/Reperfusion Damage in Diabetic Rats.Journal of personalized medicine · 2024Article
- The evolving role of GLP-1 agonists in ischemic stroke prevention in diabetic patients.Cardiovascular endocrinology & metabolism · 2024Review
- The GLP-1 receptor agonist exenatide improves recovery from spinal cord injury by inducing macrophage polarization toward the M2 phenotype.Frontiers in neuroscience · 2024Article
- Research progress on post-translational modification of proteins and cardiovascular diseases.Cell death discovery · 2023Review
- Construction and performance of exendin-4-loaded chitosan-PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats.Drug delivery · 2022Article
- Review
- RETRACTED: Long-Lasting Exendin-4-Loaded PLGA Nanoparticles Ameliorate Cerebral Ischemia/Reperfusion Damage in Diabetic Rats.Journal of personalized medicine · 2022Article
- Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research.Frontiers in neurology · 2022Review
- Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- miR-7-5p Affects Brain Edema After Intracerebral Hemorrhage and Its Possible Mechanism.Frontiers in cell and developmental biology · 2020Article
- Shear Stress Rescued the Neuronal Impairment Induced by Global Cerebral Ischemia Reperfusion via Activating PECAM-1-eNOS-NO Pathway.Frontiers in cell and developmental biology · 2020Article
- Protective Role of mTOR in Liver Ischemia/Reperfusion Injury: Involvement of Inflammation and Autophagy.Oxidative medicine and cellular longevity · 2019Review
- Brain GLP-1/IGF-1 Signaling and Autophagy Mediate Exendin-4 Protection Against Apoptosis in Type 2 Diabetic Rats.Molecular neurobiology · 2018Article
- Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction.Neural regeneration research · 2018Article
- DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways.Frontiers in pharmacology · 2018Article
- Effects of Glucagon-Like Peptide-1 on Oxidative Stress and Nrf2 Signaling.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucagon-like peptide-1 (GLP-1) receptor activation in the brain provides neuroprotection. Exendin-4 (Ex-4), a GLP-1 analog, has seen limited clinical usage because of its short half-life. We developed long-lasting Ex-4-loaded poly(D,L-lactide-co-glycolide) microspheres (PEx-4) and explored its neuroprotective potential against cerebral ischemia in diabetic rats. Compared with Ex-4, PEx-4 in the gradually degraded microspheres sustained higher Ex-4 levels in the plasma and cerebrospinal fluid for at least 2 weeks and improved diabetes-induced glycemia after a single subcutaneous administration (20 μg/day). Ten minutes of bilateral carotid artery occlusion (CAO) combined with hemorrhage-induced hypotension (around 30 mm Hg) significantly decreased cerebral blood flow and microcirculation in male Wistar rats subjected to streptozotocin-induced diabetes. CAO increased cortical O2(-) levels by chemiluminescence amplification and prefrontal cortex edema by T2-weighted magnetic resonance imaging analysis. CAO significantly increased aquaporin 4 and glial fibrillary acidic protein expression and led to cognition deficits. CAO downregulated phosphorylated Akt/endothelial nitric oxide synthase (p-Akt/p-eNOS) signaling and enhanced nuclear factor (NF)-κBp65/intercellular adhesion molecule-1 (ICAM-1) expression, endoplasmic reticulum (ER) stress, and apoptosis in the cerebral cortex. PEx-4 was more effective than Ex-4 to improve CAO-induced oxidative injury and cognitive deficits. The neuroprotection provided by PEx-4 was through p-Akt/p-eNOS pathways, which suppressed CAO-enhanced NF-κB/ICAM-1 signaling, ER stress, and apoptosis.
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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.