Abstract 5130: Leptin Increases Perihematomal Inflammation in Experimental Hemorrhagic Stroke

Abstract

Background : Leptin, one of the most alleged adipokines, exerts its tissue-protective effect in ischemic injuries by reducing apoptosis through extracellular signal-regulated kinase pathway. In this context, it may be speculated that leptin also confer beneficial effect on hemorrhagic events. However, few studies have elaborated on the association between exogenous leptin and tissue damage in experimental hemorrhagic stroke model. Methods : After inducing intracerebral hemorrhage in mouse brain via the sterotaxic infusion of collagenase, 4mg/kg or 8mg/kg of recombinant leptin or vehicle (phosphate buffered saline) was administered intraperitoneally. Brain water content, reflecting peri-hematomal edema, and hemorrhage volume were measured at 72 hours after inducing hemorrhage. Inflammatory cells expressing myeloperoxidase (MPO) or OX6 were counted at 48 hours, and western blotting for Akt, pAkt, STAT3, pSTAT3, ERK and pERK was performed at 24 hours. Results : Compared to the vehicle injected mice, exogenous leptin increased brain water contents (80.07±0.29% in vehicle group, 80.74±0.32% in 4mg/kg leptin, and 81.48±0.18% in 8mg/kg leptin; rho=0.525 and p<0.01). Based on this result, all the following experiments were performed with 8mg/kg of leptin. Leptin injection also augmented infiltration of MPO-stained cells (210±8 cells/mm 3 in leptin group and 133±8 cells/mm 3 in vehicle group; p<0.05) and OX6-stained cells (129±13 cells/mm 3 in leptin group and 88±10 cell/mm 3 in vehicle group; p<0.05). Mean hemorrhage volume was also increased in 8mg/kg leptin group (26.83±3.22 mm 3 in leptin group and 17.98±2.73 mm 3 in vehicle group; p<0.05). The expression level of phosphorylated STAT3 was significantly elevated in mice with 8mg/kg leptin injection (p<0.05), however, pAkt and pERK did not augmented by induced hyperleptinemia. Conclusion : Our study documented that peri-hematomal inflammation and hemorrhage volume were increased by exogenous leptin via STAT3 pathway. These results may indicate the potentially detrimental role of leptin on hemorrhagic stroke via augmentation of inflammatory response after tissue damage.