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

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

  • CNS Neurosci Ther. 2024 Mar;30(3):e14676. doi: 10.1111/cns.14676.
Rong-Liang Wang 1 2 3,  Zhen-Hong Yang 1,  Yu-You Huang 1,  Yue Hu 1,  Yi-Lin Wang 1,  Feng Yan 1 2 3,  Yang-Min Zheng 1 2 3,  Zi-Ping Han 1 2 3,  Jun-Fen Fan 1 2 3,  Zhen Tao 1 2 3,  Hai-Ping Zhao 1 2 3,  Si-Jie Li 2 3 4,  Yu-Min Luo 1 2 3
Affiliations

Affiliations

  • 1 Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
  • 2 Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
  • 3 Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.
  • 4 Emergency Department, Xuanwu Hospital of Capital Medical University, Beijing, China.
PMID: 38488446 DOI: 10.1111/cns.14676
Abstract

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.

Keywords

ARA290; cerebral ischemia; neuroprotection; β-Common receptor.

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