Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Erythropoietin exerts neuroprotective effect against hypoxic-ischemic brain injury in neonatal mice by activating AMPK pathway and upregulating UCP2

Weini Bian¹, Ling Zhou², Yi Jia¹, Xinting Wu¹, Yuancui Meng¹

¹Department of Neonatology, The 2nd Affiliated Hospital of Xi'an Medical University, Xi 'an 710038, Shaanxi Province, Chuna; ²Department of Obstetrics and Gynecology, Special Medical Center of the Strategic Support Force, Beijing 100101, China.

For correspondence:- Yuancui Meng Email: bianweini@163.com

Accepted: 23 December 2022 Published: 30 January 2023

Citation: Bian W, Zhou L, Jia Y, Wu X, Meng Y. Erythropoietin exerts neuroprotective effect against hypoxic-ischemic brain injury in neonatal mice by activating AMPK pathway and upregulating UCP2. Trop J Pharm Res 2023; 22(1):59-65 doi: 10.4314/tjpr.v22i1.9

© 2023 The authors.
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Abstract

Purpose: To investigate the neuroprotective effect of erythropoietin (EPO) against hypoxic-ischemic brain injury in neonatal mice, and the underlying mechanism(s) of action.

Methods: Sixty neonatal mice were assigned to 3 groups: sham, model and EPO intervention groups, each with 20 mice. Western blot assay was used to determine changes in the protein expressions of AMPK, UCP2 and KLF2. Fluorescence intensity of reactive oxygen species (ROS) was evaluated with flow cytometry.

Results: The protein expressions of AMPK and KLF2 in the cerebral tissues of EPO intervention mice were significantly up-regulated, relative to model mice (p < 0.05), while UCP2 protein level was also significantly higher in EPO intervention mice than in model mice (p < 0.05). Mean fluorescence intensity of ROS was significantly higher in the cerebral cortex of model mice than in sham mice, but it was down-regulated in the cerebral cortex of mice in EPO intervention group, relative to the model group (p < 0.05).

Conclusion: EPO exerts neuroprotective effect by activating AMPK pathway, up-regulating protein expression of UCP2, inhibiting production of mitochondrial ROS, and reducing oxidative stress in brain tissue. Thus, EPO has potentials for use in clinical practice as a neuroprotective agent.

Keywords: Hypoxic-ischemic brain injury, Erythropoietin, Adenylate-activated protein kinase, Uncoupling protein 2, Oxidative stress