Neuroprotective and neurotoxic effects of cyclosporine A on transient focal ischemia in mdr1a knockout mice

The proper dose of cyclosporine A as a neuroprotective agent was investigated using the middle cerebral artery occlusion model of mdr1a knockout mice. After a 30-min occlusion period, reperfusion was performed and the vehicle or cyclosporine A (1 mg/kg or 10 mg/kgx2) was intraperitoneally administered to each animal model group. Forty eight hours after reperfusion, infarction volume in the 1 mg/kg cyclosporine A group was significantly less than that seen in the vehicle group, although, in the high dose cyclosporine A group, infarction volumes were significantly higher than those seen in the vehicle group. These results demonstrate that cyclosporine A shows not only anti-ischemic effects, but also neurotoxic effects depending on the dosage penetrating into the brain. (C) 2004 Elsevier B.V. All rights reserved.