PMID- 37996729
OWN - NLM
STAT- Publisher
LR  - 20231123
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
DP  - 2023 Nov 24
TI  - Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of 
      Microglia via Wnt/beta-catenin Pathway in Hypoxic-Ischemic Neonatal Rats.
LID - 10.1007/s12035-023-03777-y [doi]
AB  - Inflammatory reaction plays a key role in the pathogenesis of hypoxic-ischemic 
      encephalopathy (HIE) in neonates. Microglia are resident innate immune cells in 
      the central nervous system and are profoundly involved in neuroinflammation. 
      Studies have revealed that atorvastatin exerts a neuroprotective effect by 
      regulating neuroinflammation in adult animal models of brain stroke and traumatic 
      brain injury, but its role regarding damage to the developing brain remains 
      unclear. This study aimed to clarify the effect and mechanism of atorvastatin on 
      the regulation of microglia function in neonatal hypoxic-ischemic brain damage 
      (HIBD). The oxygen glucose deprivation (OGD) of microglia and neonatal rat HIBD 
      model was established. Atorvastatin, recombinant sclerostin protein (SOST), and 
      XAV939 (degradation of beta-catenin) were administered to OGD microglia and HIBD 
      rats. The pathological changes of brain tissue, cerebral infarction volume, 
      learning and memory ability of rats, pro-inflammatory (CD16(+)/Iba1(+)) and 
      anti-inflammatory (CD206(+)/Iba1(+)) microglia markers, inflammation-related 
      indicators (Inos, Tnfalpha, Il6, Arg1, Tgfb, and Mrc1), and Wnt/beta-catenin signaling 
      molecules were examined. Atorvastatin reduced OGD-induced pro-inflammatory 
      microglia and pro-inflammatory factors, while increasing anti-inflammatory 
      microglia and anti-inflammatory factors. In vivo, atorvastatin attenuated 
      hypoxia-ischemia (HI)-induced neuroinflammation and brain damage. 
      Mechanistically, atorvastatin decreased SOST expression and activated the 
      Wnt/beta-catenin signaling pathway, and the administration of recombinant SOST 
      protein or XAV939 inhibited Wnt/beta-catenin signaling and attenuated the 
      anti-inflammatory effect of atorvastatin. Atorvastatin promotes the 
      pro/anti-inflammatory phenotypic transformation of microglia via the 
      Wnt/beta-catenin pathway in HI neonatal rats. Atorvastatin may be developed as a 
      potent agent for the treatment of HIE in neonates.
CI  - (c) 2023. The Author(s).
FAU - Yu, Luting
AU  - Yu L
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Huang, Lingyi
AU  - Huang L
AD  - Department of Orthodontics, State Key Laboratory of Oral Diseases, West China 
      College of Stomatology, Sichuan University, Chengdu, 610041, China.
FAU - Zhao, Yuanyuan
AU  - Zhao Y
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Liu, Shixi
AU  - Liu S
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Zhou, Ruixi
AU  - Zhou R
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Yue, Yan
AU  - Yue Y
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Sun, Hao
AU  - Sun H
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Su, Xiaojuan
AU  - Su X
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Liu, Qian
AU  - Liu Q
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Li, Shiping
AU  - Li S
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Ying, Junjie
AU  - Ying J
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Zhao, Fengyan
AU  - Zhao F
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China.
FAU - Qu, Yi
AU  - Qu Y
AUID- ORCID: 0000-0002-9993-8810
AD  - Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of 
      Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, 
      West China Second University Hospital, Sichuan University, Chengdu, 610041, 
      Sichuan, China. quyi712002@163.com.
LA  - eng
GR  - 81971428/Innovative Research Group Project of the National Natural Science 
      Foundation of China/
GR  - 81971429/Innovative Research Group Project of the National Natural Science 
      Foundation of China/
GR  - 2021YJ0017/Sichuan Province Science and Technology Support Program/
PT  - Journal Article
DEP - 20231124
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
SB  - IM
OTO - NOTNLM
OT  - Hypoxic ischemic
OT  - Microglia
OT  - Pro/anti-inflammatory phenotype
OT  - Sclerostin
OT  - Wnt/beta-catenin pathway
EDAT- 2023/11/24 00:42
MHDA- 2023/11/24 00:42
CRDT- 2023/11/23 23:44
PHST- 2023/02/01 00:00 [received]
PHST- 2023/11/06 00:00 [accepted]
PHST- 2023/11/24 00:42 [medline]
PHST- 2023/11/24 00:42 [pubmed]
PHST- 2023/11/23 23:44 [entrez]
AID - 10.1007/s12035-023-03777-y [pii]
AID - 10.1007/s12035-023-03777-y [doi]
PST - aheadofprint
SO  - Mol Neurobiol. 2023 Nov 24. doi: 10.1007/s12035-023-03777-y.