Cyclosporin A enhanced protection of nimodipine against brain damage induced by hypoxia-ischemia in mice and rats.

AIM: To study whether P-glycoprotein (P-gp) inhibitor cyclosporin A (CsA)
enhanced the protection of nimodipine (NMD) against brain damage.
METHOD: (1) After mice were given ip NMD alone or co-administration of CsA,
survival time of mice were recorded following decapitation and ip injection of
NaNO2, respectively. (2) After rats were given ip NMD alone or co-administration
of CsA, 20 min forebrain ischemia induced by the technique of two-carotid
occlusion plus hypovolemic hypotension. Following reperfusion of 1 h, the content
of malondialdehyde (MDA), lactic acid (LA) and activity of lactic dehydrogenase
(LDH) in cortex tissue were measured. (3) NMD level in brain was also determined
after ip injection of NMD 2 mg/kg alone and co-administration of CsA,
respectively.
RESULTS: NMD showed potent pharmacological activity in the three models. The
survival time of mice by decapitation and ip NaNO2 were significantly (P <0.05)
prolonged after co-administration of CsA. In rat forebrain ischemia/reperfusion,
levels of MDA, LA, and LDH by co-administration of CsA were greatly modified,
compared with those of NMD alone group. The level of NMD in rat brain was
increased markedly after co-administration of CsA.
CONCLUSION: P-gp inhibitor CsA may enhance the protection of NMD against brain
damage.