Pulsed focused ultrasound combined with micro-bubble contrast agent can open the blood-brain barrier of gliblastoma patients and improve the efficacy of Temozolomide treatment / 解放军医学杂志

ABSTRACT

Objective This research examined the effect ofmicrobubble contrast agent plus ultrasound on the permeability of blood-brain barrier,and explored whether it affects the efficacy of chemotherapeutic drugs on cerebral glioblastoma.Methods Wistar rats were divided into three groups to find the optimal concentration of ultrasonic contrast agent.To identify the best ultrasound mode that affected the permeability of blood brain barrier,we employed transmission electron microscopy for study of brain ultrastructure.Western blotting was used to detect the tight junction protein claudin-5.Evans blue staining of brain tissues was utilized to identify the best ultrasonic contrast agent concentration and mode.Rat glioma cells (line 9L) were injected into Wistar rats.After temozolomide chemotherapy,the tumor size was measured and the tumor marker GFAP in serum was detected by ELISA.Results The best contrast agent concentration which increases permeability of BBB in rats was found to be lml/kg and the best ultrasound mode was intermittentlytriggered pulses lasting for 10min (with interval was set at 400ms).More Evans blue passed the blood-brain barrier in ultrasonic cavitation effect group than in control group (P＜0.05).After temozolomide chemotherapy,more tumor marker GFAP was detected in ultrasonic cavitation effect group than in control group (P＜0.05).Conclusion The permeability of BBB was increased and more temozolomide went through BBB when the rats were subjected to intermittently triggered ultrasonic pulses and were injected at contrast agent at lml/kg,which could help to achieve better therapeutic efficacy for glioblastoma.