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Apelin-13 attenuates injury following ischemic stroke by targeting matrix metalloproteinases (MMP), endothelin- B receptor, occludin/claudin-5 and oxidative stress.
- Source :
-
Journal of chemical neuroanatomy [J Chem Neuroanat] 2021 Dec; Vol. 118, pp. 102015. Date of Electronic Publication: 2021 Aug 25. - Publication Year :
- 2021
-
Abstract
- Oxidative stress, an adverse consequence of brain ischemia-reperfusion injury (IRI), activates matrix metalloproteinase enzymes which cause to destruction of extracellular matrix and tight junction proteins. Oxidative stress during stroke increases serum endothelin-1 and endothelin B receptor (ETBR) expression. Apelin-13, an endogenous peptide, is expressed in numerous tissues that regulate diverse physiological and pathological processes. This study aimed to investigate the effect of intravenous (IV) injection of apelin-13 on cerebral vasogenic edema due to brain IRI. Animals were divided into sham, ischemia, and treat groups. IRI model was induced by middle cerebral artery occlusion (MCAO) for 60 min followed by 23 h reperfusion. Apelin-13 was injected into the tail vein 5 min before reperfusion. Neurological defects were evaluated with longa test. Brain water content and BBB permeability were assessed according to cerebral dry-wet weight and brain Evans blue extraction. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were measured using the colorimetric method. Expression of occludin and claudin-5, matrix metalloproteinase- 2 and 9 (MMP-2 & 9) and, ETBR were evaluated using Western blot. Brain IRI was associated with BBB breakdowns and vasogenic edema. Apelin-13 significantly reduced BBB permeability and vasogenic edema. Apelin-13 significantly attenuated IRI-related oxidative stress. Apelin-13 decreased expression of mmp-2, 9 and ETBR, prevented from decrement of occludin and claudin-5 expersion, which protected BBB integrity and reduced vasogenic edema. In conclusion, our results have suggested that an IV injection of apelin-13 could somehow reduce vasogenic edema via targeting oxidative stress and ETBR expression.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antioxidants metabolism
Brain Chemistry drug effects
Brain Edema drug therapy
Infarction, Middle Cerebral Artery drug therapy
Infusions, Intravenous
Male
Rats
Rats, Wistar
Claudin-5 antagonists & inhibitors
Intercellular Signaling Peptides and Proteins pharmacology
Intercellular Signaling Peptides and Proteins therapeutic use
Ischemic Stroke drug therapy
Matrix Metalloproteinase Inhibitors pharmacology
Matrix Metalloproteinase Inhibitors therapeutic use
Occludin antagonists & inhibitors
Oxidative Stress drug effects
Receptor, Endothelin B drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6300
- Volume :
- 118
- Database :
- MEDLINE
- Journal :
- Journal of chemical neuroanatomy
- Publication Type :
- Academic Journal
- Accession number :
- 34454018
- Full Text :
- https://doi.org/10.1016/j.jchemneu.2021.102015