Protective effect of systemic treatment with cyclosporine A after global ischemia in rats

Systemic administration of cyclosporine A (CsA) in single daily doses provides a powerful protection to the ischemic rat brain only to sites where the blood-brain barrier (BBB) is disrupted. This study was aimed at evaluating the effectiveness of prolonged treatment and multiple daily doses of systemic CsA following transient global ischemia in rats without BBB breakdown. Multiple daily doses selectively enhanced cell survival at 7-day recovery in regions displaying delayed neuronal death (DND). The effect was dose dependent, enhanced by prolonging the treatment or further fractionating daily doses, and not accompanied by drug-induced hypothermia. These results suggest that CsA-susceptible immune mediators of DND may be active during the first days following transient global ischemia. Conversely, postischemic hyperthermia may enhance and/or perpetuate similar mechanisms and trigger Alzheimer-like neurodegeneration, as recently reported.