H₂S Donor SPRC Ameliorates Ischemic Stroke by Upregulating CD24

Ischemic stroke is well-known for its high mortality and morbidity, but its treatment remains to be explored due to the current limitations. For example, severe neuroinflammation occurs after ischemic stroke; however, effective neuroinflammatory inhibitors are still lacking. Thus, the development of new therapeutic targets of inhibiting neuroinflammation is urgent. CD24 is a small heavy glycosylated protein, which plays a critical role in neural development and acts as an inflammatory suppressor in tumors and autoimmune diseases. But the role of CD24 in ischemic stroke remains unknown.

The role of CD24 in ischemic stroke should be explored. Additionally, the potential relationship between the H₂S donor, S-propargyl-cysteine (SPRC) and CD24 in ischemic stroke should be revealed.

Mechanism studies have been performed both in vitro and in vivo to verify the CD24-mediated inflammation and migration. SPRC has been applied to treat ischemic stroke, and its potential association with CD24 has been studied.

The overexpression of CD24 can inhibit the nuclear factor kappa B (NF-κB) inflammatory signaling pathway and promote the migration ability of M2 microglia cells via Src/Fak/Pyk2 signaling pathway in an inflammatory model of BV2 cells. SPRC can upregulate the level of endogenous H₂S via cystathionase-β-synthase (CBS) and it indirectly plays a role in upregulating CD24.

CD24 could be a potential target of inhibiting neuroinflammation. SPRC reduces inflammation in ischemic stroke by regulating the CD24/Iκ-Bα/NF-κB inflammatory signaling pathway and improves the migration ability of M2 microglia via CD24/Src/Fak/Pyk2 signaling pathway, which further alleviates the inflammatory response at the lesion.