Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke.

Autor: Wang RL; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China., Yang ZH; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China., Huang YY; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China., Hu Y; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China., Wang YL; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China., Yan F; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China., Zheng YM; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China., Han ZP; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China., Fan JF; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China., Tao Z; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China., Zhao HP; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China., Li SJ; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.; Emergency Department, Xuanwu Hospital of Capital Medical University, Beijing, China., Luo YM; Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.
Jazyk: angličtina
Zdroj: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2024 Mar; Vol. 30 (3), pp. e14676.
DOI: 10.1111/cns.14676
Abstrakt: Aim: To explore the neuroprotective effects of ARA290 and the role of β-common receptor (βCR) in a mouse model of middle cerebral artery occlusion (MCAO).
Methods: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and βCR were measured by western blot.
Results: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against βCR.
Conclusion: ARA290 provided a neuroprotective effect via βCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.
(© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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