1. Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation.
- Author
-
Chen J, Zhang C, Yan T, Yang L, Wang Y, Shi Z, Li M, and Chen Q
- Subjects
- Animals, Brain metabolism, Brain pathology, Brain Edema etiology, Brain Edema metabolism, Brain Edema pathology, Brain Edema prevention & control, Brain Injuries etiology, Brain Injuries metabolism, Brain Injuries pathology, Case-Control Studies, Caspase 1 metabolism, Cell Line, Cytokines metabolism, DNA-Binding Proteins metabolism, Disease Models, Animal, Encephalitis etiology, Encephalitis metabolism, Encephalitis pathology, Hemin toxicity, Humans, Inflammation Mediators metabolism, Interleukin-18 metabolism, Interleukin-1beta metabolism, Male, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Neurons metabolism, Neurons pathology, Subarachnoid Hemorrhage complications, Subarachnoid Hemorrhage metabolism, Subarachnoid Hemorrhage pathology, Mice, Atorvastatin pharmacology, Brain drug effects, Brain Injuries prevention & control, Encephalitis prevention & control, Neurons drug effects, Neuroprotective Agents pharmacology, Pyroptosis drug effects, Subarachnoid Hemorrhage drug therapy
- 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., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
- View/download PDF