Schematic representation of signaling pathways pSTAT3 and pSmad2 effects in the CA1 region after IR injury, in response to LepA IA injection via ipsilateral ICA at reperfusion.

(A) Without treatment, leptin overexpression induced by IR injury attaches to upregulated LepRs to form an active complex, while following LepA IA treatment most LepRs are occupied by LepA molecules. (B) Without LepA treatment the leptin-LepR complex (black arrows) induces pSTAT3 upregulation and subsequent caspase3 expression (apoptosis) and inflammation. The outcome of this cascade is increased cell death. However, LepA treatment (blue arrows), prevents leptin-LepR complex formation, resulting in reduced pSTAT3, caspase3, and inflammation. Subsequently, the outcome of LepA treatment at reperfusion is neuronal cell preservation.