Neuroprotective Effects of Cyclosporine in a Porcine Pre-Clinical Trial of Focal Traumatic Brain Injury

Abstract Mitochondrial dysfunction is thought to be a hallmark of traumatic brain injury (TBI) and plays a pivotal role in the resulting cellular injury. Cyclophilin D–mediated activation of the mitochondrial permeability transition pore has been suggested to contribute to this secondary injury cascade. Cyclosporine possesses neuroprotective properties that have been attributed to the desensitization of mitochondrial permeability transition pore activation. In vivo animal experiments have demonstrated neuroprotective effects of cyclosporine in more than 20 independent experimental studies in a multitude of different experimental models. However, the majority of these studies have been carried out in rodents. The aim of the present study was to evaluate the efficacy of a novel and cremophor/kolliphor EL–free lipid emulsion formulation of cyclosporine in a translational large animal model of TBI. A mild-to-moderate focal contusion injury was induced in piglets using a controlled cortical impact device. Afte...