Volume 36, Issue 4 e22263
RESEARCH ARTICLE
Free to Read

Atorvastatin inhibits neuronal apoptosis via activating cAMP/PKA/p-CREB/BDNF pathway in hypoxic-ischemic neonatal rats

Luting Yu

Luting Yu

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Shixi Liu

Shixi Liu

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Ruixi Zhou

Ruixi Zhou

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Hao Sun

Hao Sun

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Xiaojuan Su

Xiaojuan Su

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Qian Liu

Qian Liu

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Shiping Li

Shiping Li

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Junjie Ying

Junjie Ying

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Fengyan Zhao

Fengyan Zhao

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

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Dezhi Mu

Corresponding Author

Dezhi Mu

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

Correspondence

Yi Qu and Dezhi Mu, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Email: [email protected] and [email protected]

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Yi Qu

Corresponding Author

Yi Qu

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

Correspondence

Yi Qu and Dezhi Mu, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Email: [email protected] and [email protected]

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First published: 18 March 2022
Citations: 6

Luting Yu and Shixi Liu contributed equally to this manuscript.

Abstract

Neuronal apoptosis is one of the main pathological processes of hypoxic-ischemic brain damage (HIBD) and is involved in the development of hypoxic-ischemic encephalopathy (HIE) in neonates. Atorvastatin has been found to have neuroprotective effects in some nervous system diseases, but its role in regulating the pathogenesis of neonatal HIBD remains elusive. Thus, this study aimed to explore the effects and related mechanisms of atorvastatin on the regulation of neuronal apoptosis after HIBD in newborn rats. The rat HIBD model and the neuronal oxygen glucose deprivation (OGD) model were established routinely. Atorvastatin, cAMP inhibitor (SQ22536), and BDNF inhibitor (ANA-12) were used to treat HIBD rats and OGD neurons. Cerebral infarction, learning and memory ability, cAMP/PKA/p-CREB/BDNF signaling molecules, and apoptosis-related indicators (TUNEL, cleaved caspase-3, and Bax/Bcl2) were then examined. In vivo, atorvastatin reduced cerebral infarction, improved learning and memory ability, decreased the number of TUNEL-positive neurons, inhibited the expression of cleaved caspase-3 and Bax/Bcl2, and activated the cAMP/PKA/p-CREB/BDNF pathway in the cerebral cortex after HIBD. In vitro, atorvastatin also decreased the apoptosis-related indicators and activated the cAMP/PKA/p-CREB/BDNF pathway in neurons after OGD. Furthermore, inhibition of cAMP or BDNF attenuated the effect of atorvastatin on the reduction of neuronal apoptosis, suggesting that atorvastatin inhibits HIBD-induced neuronal apoptosis and alleviates brain injury in neonatal rats mainly by activating the cAMP/PKA/p-CREB/BDNF pathway. In conclusion, atorvastatin may be developed as a potential drug for the treatment of neonatal HIE.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author.