A protective effect of a mitochondria-targeted antioxidant, a cationic rhodamine derivative linked to a plastoquinone molecule (10-(6'-plastoquinonyl)decylrhodamine-19, SkQR1) was studied in the model of open focal trauma of rat brain sensorimotor cortex. It was found that daily intraperitoneal injections of SkQR1 (100 nmol/kg) for 4 days after the trauma improved performance in a test characterizing neurological deficit and decreased the volume of the damaged cortical area. Our results suggest that SkQR1 exhibits profound neuroprotective effect, which may be explained by its antioxidative activity.

BackgroundMany ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies.Methodology/Principal FindingsWe used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β) in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s) which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated kidney cells with cortical neurons resulted in enchanced phosphorylation of GSK-3β in neuronal cells.ConclusionThe results indicate that renal preconditioning and SkQR1-induced brain protection may be mediated through the release of EPO from the kidney.

ObjectivesCold crystalloid cardioplegia for donor heart harvesting and cold ischemic storage conditions during the transportation is the standard of care during heart transplantation procedure. Organ care system (OCS) was introduced for more prolonged and reliable ex vivo organ management. This study evaluated the two different techniques used for myocardial preservation during the procurement and transportation of the heart using the OCS.MethodsWe performed prospective analysis of 43 patients with heart failure undergoing heart transplantation and using the OCS for donor organ transport. Donor hearts were arrested using blood cardioplegia and conditioning (n = 30) or standard Custodiol (SC) solution ( n = 13). Perfusion and cardiac function parameters were continuously monitored while the donor hearts were perfused in the OCS. Impact of preservation techniques on biochemical parameters and clinical outcomes were evaluated.ResultsAll donor hearts had stable perfusion and lactate characteristics in the OCS, with similar measures between the two groups at the beginning of the ex vivo perfusion. Ex vivo heart perfusion mean ending concentration of Interleukin (IL)‐6 and IL‐8 was significantly lower in the blood cardioplegia group compared to the standard care group. Clinical outcomes were comparable between the two groups of patients.ConclusionsThe use of blood cardioplegia and conditioning could be a safe method for myocardial protection in distant procurement and preservation of donor hearts in the OCS.