Neurotoxicity of Paclitaxel and Rapamycin in a Rat Model with Transient Blood-Brain Barrier Opening

Abstract

Objective : Drug-eluting stents and balloons are occasionally used to reduce restenosis in medically intractable intracranial atherosclerotic stenosis. The authors aimed to determine whether such drugs can cause neurotoxicity due to local effects in a rat model.Methods : Intra-arterial catheters were placed in the right common carotid artery of rats. Mannitol was injected to transiently open the brain-blood barrier (BBB), followed by high-dose drug (paclitaxel and rapamycin) injection. The optimal time interval of transient BBB opening for maximal drug penetration was determined to be 10 minutes. Paclitaxel and rapamycin were intraarterially administered in various doses. All the rats were neurologically evaluated, and their brain tissues were histologically examined.Results : Neither neurological deficits nor histological abnormalities were observed in all the rats.Conclusion : Paclitaxel and rapamycin did not cause neurotoxicity in a rat model with transient BBB opening.