TREATMENT OF ISCHEMIC STROKE BY TARGETING SODIUM-POTASSIUM-ATPASE AND HYDROGEN SULFIDE

Abstract

EVIDENCES SUGGEST THAT MODULATING NA-K-ATPASE (NKA) AND HYDROGEN SULFIDES ARE POTENTIAL THERAPEUTIC STRATEGIES OF ISCHEMIC STROKE. WE DEVELOPED A SITE-SPECIFIC ANTIBODY (DR-AB), WHICH CAN ACTIVATE NKA WHEN IT BINDS TO AN EXTRACELLULAR REGION 897DVEDSYGQQWTYEQR911 (DR REGION) OF NKA. WE ALSO SYNTHESIZED A HYDROGEN SULFIDE RELEASING COMPOUND ADTOH-DANSHENSU (ADTOH-DSS). I EXAMINED THE EFFECTS OF THESE TWO POTENTIAL NEUROPROTECTANTS IN ISCHEMIC STROKE USING BOTH IN VITRO AND IN VIVO MODELS. MY RESULTS SHOWED THAT BOTH PRE- AND POST-TREATMENT WITH DR-AB HAD PROTECTIVE EFFECTS IN MICE SUBJECTED TO TRANSIENT MIDDLE CEREBRAL ARTERY OCCLUSION. THESE BENEFICIAL EFFECTS WERE ACCOMPANIED WITH RESTORED NKA ACTIVITY, IMPROVED CA2+ HANDLING, DECREASED APOPTOSIS AND SUPPRESSED INFLAMMATION. ADTOH-DSS PRETREATMENT PROTECTED SH-SY5Y CELLS FROM OGD/R-INDUCED INJURIES BUT FAILED TO EXERT PROTECTIVE EFFECTS IN TMCAO MICE. IN SUMMARY, THE CURRENT STUDY SHOWED THAT STIMULATING NKA WITH THE DR-SPECIFIC ANT