Effect of intracranial Cryptococcus neoformans infection on the function of efflux transporter breast cancer-resistance protein / 解放军医学杂志

ABSTRACT

Objective To explore the effect of intracranial Cryptococcus neoformans (Cr.neoformans) infection on the function of fluconazole transport by breast cancer-resistance protein (BCRP),a kind of efflux transporter on the blood-brain barrier (BBB).Methods Twenty-four male Sprague-Dawley rats were randomly divided into 4 groups (6 each)normal rats received 20mg/kg fluconazole by intravenous injection (Group A),normal rats received 20mg/kg fluconazole with co-administration of pantoprazole (a kind of BCRP inhibitor) by intravenous injection (Group B),rats with intracranial Cr.neoformans infection received 20mg/kg fluconazole (Group C),and infected rats received 20mg/kg fluconazole with co-administration of pantoprazole (Group D).Microdialysis probes were implanted into the rats' striatum to continuously collect brain extracellular fluid (ECF) after the intravenous infusion of fluconazole with or without BCRP inhibitor pantoprazole.High-performance liquid chromatography (HPLC) was applied to measure the fluconazole concentrations in blood and brain ECF.The area under the concentration-time curves of fluconazole and the penetration of fluconazole passing though BBB were then calculated.Results Meningoencephalitis rat model was successfully established by intracerebral inoculation of Cr.neoformans.The infection significantly increased the penetration of fluconazole passing through BBB (P＜0.05).Pantoprazole did not alter the distribution of fluconazole in normal rat's brain,but significantly increased the penetration of fluconazole passing through BBB of the infected rats (P＜0.05).Conclusion Cr.neoformans infection can reduce the BBB resistance to fluconazole,and induce the efflux transport of fluconazole from the brain ECF back into the blood by BCRP.