The Influence Of Intracranial Cryptococcus Gattii Infection On Brain Barrier Permeability And Study Of Brain Barrier Transport Mechanism Of MRPs In Rats With Cryptococcal Meningitis

Objective:1. To establish rats model of cryptococcus gattii meningitis (CM);2. To compare the permeability of the blood - brain barrier (BBB) and blood -cerebrospinal fluid barrier (BCSFB) in cryptococcus gattii meningitis (CM) rats ;3. To compare the permeability of the blood - brain barrier and blood - cerebrospinal fluid barrier in cryptococcus gattii meningitis (CM) rats and normal rats.4. To observe the effect on the permeability of the blood - brain barrier (BBB) and the blood - cerebrospinal fluid barrier (BCSFB) in normal and cryptococcus gattii meningitis rats.Methods:1. 43 rats, rats model of cryptococcus gattii meningitis (CM) were established by inoculation of Cryptococcus spp:Group A (10 rats): 10 μL fungus bacteria suspension (1 × 107CFU / ML)Group B (10 rats): 10 μL fungus bacteria suspension (1× 107CFU / ML) +hydrocortisone Group C (10 rats): 10 μL fungus bacteria suspension (1 × 108CFU / ML)Group D (10 rats): 10 μL fungus bacteria suspension (1 × 108CFU / ML) +hydrocortisone Group E (3 rats): 10 μL saline2. 6 normal rats; 12 CM rats were randomly divided into two groups (n = 6).Group A (normal rats): given fluconazole;Group B (cryptococcus gattii meningitis rats): given fluconazole;Group C (cryptococcus gattii meningitis rats): given fluconazole + probenecid.3. The concentration of fluconazole in plasma, CSF, and bECF was calculated by microdialysis and high performance liquid chromatography (HPLC) after a single intravenous (IV) injection of fluconazole (FCZ) (10 mg / kg) and probenecid. The study intends to calculate area under the curve of drug concentration - time curve and the permeability of the blood - brain barrier and blood - cerebrospinal fluid barrier in CM rats, then we analyze the distribution of FCZ and transport mechanism of MRPs.Results:1. In the process of building models, the success rate at the level of 1 ×108 CFU/ML is the highest; in the same concentration of bacterial suspension, there was no significant difference in the success rates with hydrocortisone.2. The permeability of BBB and BCSFB in cryptococcus gattii meningitis rats was 78.18 ± 2.45% VS 87.29 ± 7.11 % (P <0.05).3. Cryptococcus gattii meningitis rats + fluconazole vs normal rats + fluconazole The permeability of BBB and BCSFB in meningitis rats were increased by 16.06%(P <0.05) and 17.96% (P <0.05)4. Cryptococcus gattii meningitis rats + fluconazole + probenecid (group C) vs cryptococcus gattii meningitis rats + fluconazole (group B)The permeability of BBB in group C was 8.87% higher than that in group B (P<0.05), and there was no significant difference in BCSFB permeability.Conclusion:1. Cryptococcus gattii meningitis model was established successfully and hydrocortisone did not affect the success rate of the establishment of the cryptococcus C. gattii meningitis model.2. The permeability of BBB and BCSFB in cryptococcus gattii meningitis rats was significantly different and the permeability of BCSFB is higher than BBB.3. The permeability of BBB and BCSFB in cryptococcus gattii meningitis rats was higher than that in normal rats.4. MRPs’ inhibitor can increase the permeability of BBB in cryptococcus gattii meningitis, indicating that MRPs are involved in the transportation of fluconazole meningitis, indicating that MRPs are involved in the transportation of fluconazole via BBB in rat brain.5. There was no statistically significant change in the permeability of in BCSFB cryptococcus gattii meningitis rats, indicating that MRPs did not play a major role in the transportation of fluconazole via BCSFB in rat brain.