Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus

Although cyclosporin A and tacrolimus are used clinically as potent immunos uppressants, there have been reports of neurotoxicity and encephalopathy. A possible mechanism is that these drugs damage the blood-brain barrier (BBB ), inducing dysfunction and increased permeability, and are then able to en ter the brain. We studied the cytotoxicity of cyclosporin A and tacrolimus, focused on apoptosis induction, using an immortalized cell line establishe d from BALB/c mouse cerebral microvessel endothelial cells (MBEC4). We foun d that these two drugs induced cell shrinkage, chromatin condensation and D NA fragmentation, which are characteristics of apoptosis. Our data suggest that the induction of apoptosis on the brain capillary endothelial cells ma y be at least partly involved in the occurrence of immunosuppressant-induce d encephalopathy.