期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 236, 期 10, 页码 6920-6931出版社
WILEY
DOI: 10.1002/jcp.30351
关键词
atorvastatin; early brain injury; neuroinflammation; pyroptosis; subarachnoid hemorrhage
资金
- Natural Science Foundation of Jiangsu Province [BK20201140]
- National Natural Science Foundation of China [81871589, 81971870]
- Wuxi Municipal Bureau on Science and Technology [N20201008]
- Top Talent Support Program for young and middle-aged people of Wuxi Health Committee [HB2020119]
Atorvastatin treatment improved neurological outcomes in rats by inhibiting neural pyroptosis and neuroinflammation, reducing neuron death and increasing survival rate and neurological scores following SAH.
Subarachnoid hemorrhage (SAH) is a subtype of stroke with high mortality and morbidity due to the lack of effective therapy. Atorvastatin has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH) via reducing reactive oxygen species, antiapoptosis, regulated autophagy, and neuroinflammation. Which was the related to the pyroptosis? Pyroptosis can be defined as a highly specific inflammatory programmed cell death, distinct from classical apoptosis and necrosis. However, the precise role of pyroptosis in atorvastatin-mediated neuroprotection following SAH has not been confirmed. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of atorvastatin in the SAH-induced EBI via regulating neural pyroptosis using the filament perforation model of SAH in male C57BL/6 mice, and the hemin-induced neuron damage model in HT-22. Atorvastatin or vehicle was administrated 2 h after SAH and hemin-induced neuron damage. The mortality, neurological score, brain water content, and neuronal death were evaluated. The results show that the atorvastatin treatment markedly increased survival rate, neurological score, greater survival of neurons, downregulated the protein expression of NLRP1, cleaved caspase-1, interleukin-1 beta (IL-1 beta), and IL-18, which indicated that atorvastatin-inhibited pyroptosis and neuroinflammation, ameliorated neuron death in vivo/vitro subjected to SAH. Taken together, this study demonstrates that atorvastatin improved the neurological outcome in rats and reduced the neuron death by against neural pyroptosis and neuroinflammation.
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