Temporal patterns and distribution of pyroptosis-related molecules and effects of human mesenchymal stem cells on pyroptosis following cerebral ischemia/reperfusion in rats

• DOI: 10.1016/j.jstrokecerebrovasdis.2023.107199
• Publication Date: 2023-05-31T16:11:05Z
• Authors: Kuang Pan; Qingxia Peng; Zejia Huang; Zhaofei Dong; Weijye Lin; Yidong Wang
• Keywords: Pyroptosis; Proinflammatory cytokine

Pyroptosis is a new type of programmed cell death that has a strong proinflammatory effect. The present study investigated the dynamic changes of pyroptosis-related molecules and the effect of mesenchymal stem cells (MSCs) on pyroptosis following cerebral ischemia/reperfusion (I/R).The temporal pattern and cellular distribution of caspase-1, Gasdermin D and E (GSDMD and GSDME) in the peri-infarct area, and the effect of human MSCs on GSDMD, IL-1β, IL-18, Lactate dehydrogenase (LDH) and neurological function were studied in a rat model of transient focal cerebral ischemia.The expression of caspase-1 mRNA increased with time, with a protein level of pro-caspase-1 comparable to its mRNA level, while the level of cleaved-caspase-1 protein peaked at 48 h following I/R. Increased levels of GSDMD mRNA and protein were also observed, with a peak level at 24 h. There were no significant changes in GSDME mRNA or protein expression after I/R. In regards to changes in the number of cells expressing GSDMD after I/R, that for neurons was more significant than those for microglia and astrocytes. The modified neurological severity score discrepancy and the expression of GSDMD showed no significant differences within 24 h following I/R between the MSC- and NS-treated groups, but MSCs treatment promoted the secretion of IL-1β, IL-18 and LDH.In the early stage of cerebral infarction in rats, there were dynamic changes in pyroptosis-related molecules (caspase-1 and GSDMD), but MSCs showed no effect on the levels of GSDMD or neurological function.