As the most common cerebrovascular disease,ischemic stroke has the characteristics of high incidence,high mortality,high disability rate,and high recurrence rate,which brings a heavy burden to patients,families,and society.The main purpose of its treatment is to timely open blood vessels to restore perfusion,rescue ischemic penumbra,and im-prove neurological function.Research on the pathophysiological mechanism and treatment of ischemic stroke has always been a hot spot.A large number of studies have shown that neuroinflammation is an important mechanism of ischemic stroke.As an inflammatory cell death mode,pyroptosis is closely related to a variety of diseases and injury mechanisms,including the occurrence and development of ischemic stroke.There are a variety of key proteins in the process of pyrop-tosis,such as inflammasome,caspase-1,and Gasdermin D(GSDMD).GSDMD,as the executive protein of pyroptosis,can punch holes in the cell membrane,causing inflammatory factors such as IL-1β and IL-18 to be released into the ex-tracellular space to produce an inflammatory response.Recent studies have found that GSDMD can not only punch holes in the cell membrane but also destroy the mitochondrial membrane by punching holes,leading to impaired mitochondrial function and release of mitochondrial content.The mitochondrial membrane damage occurs before the cell membrane dam-age,which not only expands the pyroptosis process but also induces cell death through other pathways.Therefore,inhibi-ting the perforating function of GSDMD and improving the mitochondrial function of ischemic cells through mitochondrial transplantation can effectively inhibit the inflammatory response and improve the function of the ischemic penumbra,thus playing a neuroprotective role.In this review,we briefly introduce the process of pyroptosis and the mechanism of GSD-MD drilling in the process of pyroptosis,focusing on the process of mitochondrial pyroptosis and its related research pro-gress in ischemic stroke,and looking for new ideas for the treatment of ischemic stroke.
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