S. Kochi et al., Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus, LIFE SCI, 66(23), 2000, pp. 2255-2260
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.