Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Edaravone mitigates cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome via regulation of cAMP/PKA-CREB pathway

Yongmei Zhao¹, Hongli Li², Yong Chen¹, Kexing Li², Sufei Yang³

¹Department of Paediatrics, Longquanyi District of Chengdu Maternity & Child Health Care Hospital, Chengdu 610100, China; ²Department of Neonatology, Longquanyi District of Chengdu Maternity & Child Health Care Hospital, Chengdu 610100, China; ³Department of Child Health Care, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.

For correspondence:- Sufei Yang Email: fpudr3@163.com

Accepted: 22 October 2021 Published: 30 November 2021

Citation: Zhao Y, Li H, Chen Y, Li K, Yang S. Edaravone mitigates cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome via regulation of cAMP/PKA-CREB pathway. Trop J Pharm Res 2021; 20(11):2299-2304 doi: 10.4314/tjpr.v20i11.10

© 2021 The authors.
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Abstract

Purpose: To investigate the influence of edaravone on cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome (OSAHS), and the mechanism involved.

Methods: Fifty-four young Wistar rats were randomly selected into control, intermittent hypoxia and edaravone groups. The contents of the antioxidants CAT, Mn-SOD, Cu/Zn SOD and oxidative stress products malondialdehyde (MDA) in hippocampus were assayed and compared. The expressions of brain-derived neurotrophic factor (BDNF), Bcl-2, CREB, p-CREB and PKAc were determined.

Results: The times taken to cross the target quadrant and the platform; levels of CAT and Mn-SOD, as well as protein levels of BNDF, Bcl-2, p-CREB and PKAc were markedly lower in intermittent hypoxia group than in controls; and MDA contents, 8-OHdG and protein hydroxyl were markedly higher in intermittent hypoxic rats group than in controls. Time taken to cross the platform and quadrant; activities of CAT and Mn-SOD, and protein concentrations of BDNF, Bcl-2, p-CREB and PKAc were markedly higher in the edaravone-treated rats than in intermittent hypoxia rats.

Conclusion: Edaravone significantly mitigated cognitive damage and hippocampal lesions in OSAHS rats via a mechanism related to alleviation of oxidative stress and up-regulation of the expressions of p-CREB and its downstream proteins BDNF and Bcl-2. This finding provides a theoretical basis for research and development of new drugs against OSAHS.

Keywords: Obstructive sleep apnea hypopnea syndrome, Edaravone, cAMP, PKA, CREB