H₂S Donor SPRC Ameliorates Ischemic Stroke by Upregulating CD24

Area of Science:

• Neuroscience
• Immunology
• Biochemistry

Background:

• Ischemic stroke causes significant mortality and morbidity, with limited treatment options.
• Neuroinflammation is a key pathological feature of ischemic stroke, necessitating novel therapeutic targets.
• CD24, an inflammatory suppressor in other diseases, has an unknown role in ischemic stroke.

Purpose of the Study:

• To investigate the role of CD24 in ischemic stroke.
• To explore the relationship between the hydrogen sulfide (H2S) donor, S-propargyl-cysteine (SPRC), and CD24 in ischemic stroke.

Main Methods:

• In vitro and in vivo studies were conducted to examine CD24-mediated inflammation and cell migration.
• Mechanism studies focused on the effects of SPRC on endogenous H2S levels and CD24 expression.
• The study utilized BV2 cell models to analyze inflammatory signaling pathways.

Main Results:

• CD24 overexpression inhibited the nuclear factor kappa B (NF-κB) pathway and promoted M2 microglia migration via the Src/Fak/Pyk2 pathway.
• SPRC increased endogenous H2S levels via cystathionine-β-synthase (CBS), indirectly upregulating CD24.
• These findings suggest CD24 plays a crucial role in mitigating neuroinflammation post-stroke.

Conclusions:

• CD24 is a potential therapeutic target for inhibiting neuroinflammation in ischemic stroke.
• SPRC alleviates ischemic stroke inflammation by modulating the CD24/Iκ-Bα/NF-κB pathway.
• SPRC enhances M2 microglia migration via the CD24/Src/Fak/Pyk2 pathway, reducing lesion inflammation.