Abstract 15266: Nanoparticle-Mediated Simultaneous Targeting of Mitochondria and Inflammatory Monocytes Attenuates Cerebral Ischemia-Reperfusion Injury in Mice

Introduction: The early reperfusion is a principal therapeutic strategy for the treatment of acute cerebral infarction. Opening of mitochondrial permeability transition pore (mPTP), regulated by cyclophilin D (CyD), promotes inflammation and reperfusion injury. However, clinical efficacies of cyclosporine A (CsA) and statins, which can target CyD and inflammation respectively, are insufficient. Therefore, we hypothesized a simultaneous targeting of mPTP and inflammation would enhance neuroprotection after cerebral IR. To facilitate drug delivery to the ischemic tissue, we used polymeric nanoparticles composed of poly (lactic-co-glycolic acid) (PLGA-NP). Methods and Results: The middle cerebral arteries were occluded by monofilament suture and blood flow was restored 60 minutes later in CyD knockout (CyD-KO), CCR2-KO and CyD/CCR2-double KO (DKO) mice. Infarct size was decreased in CyD-KO and CCR2-KO, and additively decreased in DKO mice (Fig.A). Recruitment of Ly6Chigh monocytes was abrogated by CCR2-KO, b...