apelin-13-peptide and Ischemic-Stroke

The precise mechanisms whereby apelin-13 acts against ischemic stroke have remained in the dark. Hence, this study aims to examine the effects of apelin-13 on hypothalamic-pituitary-adrenal (HPA) axis over activation, Jak2-STAT3 signaling pathway, and inflammation following ischemic stroke.. Middle cerebral artery occlusion (MCAO) was used to induce the cerebral ischemic/reperfusion injury (I/RI). Thirty-five male Wistar rats (250-300 g, 8 weeks old) were randomly divided into sham, MCAO, and intravenous (IV) apelin-13 treated groups which received 10, 20, and 40 µg/kg 5 min before reperfusion (n = 7). Neurological status (modified Longa scoring scale), infarct volume, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin 6 (IL-6), corticosterone, and the expressions of the Jak2/STAT3 were assessed.. Our results confirm that IV administration of all three doses of apelin-13 significantly improved neurological defects and reduced infarct volume following cerebral I/RI. Furthermore, we observed that acute stroke caused a rise in the expression of the Jak2/STAT3, IL-6, corticosterone, and MDA content, while apelin-13 could reduce the expression of the Jak2/STAT3 and the serum indices in a dose-dependent manner. The 40 µg/kg dose of apelin-13 was also more effective in reducing the infarct volume and improving TAC.. Our findings suggest that apelin-13 has protective effects against cerebral I/RI-related inflammation and also could attenuate the HPA axis over activation.

Topics: Animals; Brain Ischemia; Corticosterone; Hypothalamo-Hypophyseal System; Infarction, Middle Cerebral Artery; Inflammation; Interleukin-6; Ischemic Stroke; Janus Kinase 2; Male; Pituitary-Adrenal System; Rats; Rats, Wistar; Reperfusion Injury; Signal Transduction

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.

Topics: Animals; Antioxidants; Brain Chemistry; Brain Edema; Claudin-5; Infarction, Middle Cerebral Artery; Infusions, Intravenous; Intercellular Signaling Peptides and Proteins; Ischemic Stroke; Male; Matrix Metalloproteinase Inhibitors; Occludin; Oxidative Stress; Rats; Rats, Wistar; Receptor, Endothelin B