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Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation
- Source :
- Journal of Cellular Physiology. 236:6920-6931
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- 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-1β (IL-1β), 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.
- Subjects :
- Male
0301 basic medicine
Programmed cell death
Subarachnoid hemorrhage
Physiology
Atorvastatin
Interleukin-1beta
Clinical Biochemistry
Perforation (oil well)
Brain Edema
Pharmacology
Neuroprotection
Cell Line
03 medical and health sciences
0302 clinical medicine
NLR Family, Pyrin Domain-Containing 3 Protein
Pyroptosis
Animals
Humans
Medicine
cardiovascular diseases
Neuroinflammation
Neurons
business.industry
Caspase 1
Interleukin-18
Brain
Cell Biology
Subarachnoid Hemorrhage
medicine.disease
nervous system diseases
DNA-Binding Proteins
Mice, Inbred C57BL
Disease Models, Animal
Neuroprotective Agents
030104 developmental biology
Brain Injuries
Case-Control Studies
030220 oncology & carcinogenesis
Cytokines
Encephalitis
Hemin
Inflammation Mediators
business
Neuron death
medicine.drug
Subjects
Details
- ISSN :
- 10974652 and 00219541
- Volume :
- 236
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi.dedup.....12c3736f78b1ffb94fba0b936f3cf2f9