Glucagon-like peptide-1 (GLP-1) receptor activation dilates cerebral arterioles, increases cerebral blood flow, and mediates remote (pre)conditioning neuroprotection against ischaemic stroke
| العنوان: | Glucagon-like peptide-1 (GLP-1) receptor activation dilates cerebral arterioles, increases cerebral blood flow, and mediates remote (pre)conditioning neuroprotection against ischaemic stroke |
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| المؤلفون: | Philippa Chapman, Sean M. Davidson, Stefan Trapp, Isabel N. Christie, Shereen Nizari, Derek M. Yellon, Nils Korte, Alla S. Korsak, Marina Basalay, Alexander V. Gourine, Shefeeq M. Theparambil, Frank Reimann |
| المساهمون: | Gourine, Alexander V [0000-0003-3068-491X], Apollo - University of Cambridge Repository, Reimann, Frank [0000-0001-9399-6377], Basalay, Marina [0000-0001-5608-3878], Yellon, Derek M [0000-0001-7791-9320], Gourine, Alexander V. [0000-0003-3068-491X] |
| المصدر: | Basic Research in Cardiology |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, middle cerebral artery occlusion, Physiology, Vasodilator Agents, Glucagon-like peptide-1, Perfusion scanning, 030204 cardiovascular system & hematology, Pharmacology, Rats, Sprague-Dawley, 0302 clinical medicine, Brain arterioles, Medicine, Ischemic Preconditioning, Stroke, digestive, oral, and skin physiology, Remote Ischaemic preconditioning, Infarction, Middle Cerebral Artery, Original Contribution, Cerebral blood flow, Hindlimb, 3. Good health, Vasodilation, Arterioles, Neuroprotective Agents, medicine.anatomical_structure, Cerebral cortex, Cerebrovascular Circulation, Systemic administration, neuroprotection, Cardiology and Cardiovascular Medicine, hormones, hormone substitutes, and hormone antagonists, Agonist, endocrine system, Brain Capillaries, medicine.drug_class, Ischemia, Incretins, Neuroprotection, Glucagon-Like Peptide-1 Receptor, Remote ischaemic preconditioning, 03 medical and health sciences, Physiology (medical), Animals, Ischaemic Stroke, Ischemic Stroke, business.industry, medicine.disease, Peptide Fragments, Disease Models, Animal, Regional Blood Flow, business, 030217 neurology & neurosurgery |
| الوصف: | Stroke remains one of the most common causes of death and disability worldwide. Several preclinical studies demonstrated that the brain can be effectively protected against ischaemic stroke by two seemingly distinct treatments: remote ischaemic conditioning (RIC), involving cycles of ischaemia/reperfusion applied to a peripheral organ or tissue, or by systemic administration of glucagon-like-peptide-1 (GLP-1) receptor (GLP-1R) agonists. The mechanisms underlying RIC- and GLP-1-induced neuroprotection are not completely understood. In this study, we tested the hypothesis that GLP-1 mediates neuroprotection induced by RIC and investigated the effect of GLP-1R activation on cerebral blood vessels, as a potential mechanism of GLP-1-induced protection against ischaemic stroke. A rat model of ischaemic stroke (90 min of middle cerebral artery occlusion followed by 24-h reperfusion) was used. RIC was induced by 4 cycles of 5 min left hind limb ischaemia interleaved with 5-min reperfusion periods. RIC markedly (by ~ 80%) reduced the cerebral infarct size and improved the neurological score. The neuroprotection established by RIC was abolished by systemic blockade of GLP-1R with a specific antagonist Exendin(9–39). In the cerebral cortex of GLP-1R reporter mice, ~ 70% of cortical arterioles displayed GLP-1R expression. In acute brain slices of the rat cerebral cortex, activation of GLP-1R with an agonist Exendin-4 had a strong dilatory effect on cortical arterioles and effectively reversed arteriolar constrictions induced by metabolite lactate or oxygen and glucose deprivation, as an ex vivo model of ischaemic stroke. In anaesthetised rats, Exendin-4 induced lasting increases in brain tissue PO2, indicative of increased cerebral blood flow. These results demonstrate that neuroprotection against ischaemic stroke established by remote ischaemic conditioning is mediated by a mechanism involving GLP-1R signalling. Potent dilatory effect of GLP-1R activation on cortical arterioles suggests that the neuroprotection in this model is mediated via modulation of cerebral blood flow and improved brain perfusion. |
| وصف الملف: | application/pdf; text/xml |
| تدمد: | 1435-1803 0300-8428 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba2ff9676137cd5de12a1eceda016983Test https://doi.org/10.1007/s00395-021-00873-9Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ba2ff9676137cd5de12a1eceda016983 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14351803 03008428 |
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