In Sook Lee1, Hak Jin Kim1, Seon Hee Choi1, Yong-Woo Kim2, Ki Joo Choi3. 1. Department of Radiology, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea. 2. Pusan National University Yangsan Hospital, Yangsan, South Korea. 3. Department of Biosafety Evaluation and Control, Korea National Institute of Health, Cheongju, South Korea.
Abstract
Aim: The purpose of this study was to assess changes in doxorubicin concentration in rabbit brain with respect to time after BBB opening induced by triolein emulsion infusion via a carotid artery and the mechanism of BBB opening.Materials and Methods: Doxorubicin (2.4 mg/kg) was infused immediately after triolein emulsion (1%) into rabbit carotid arteries. Bilateral hemispheres were harvested 2, 4, 6 12 and 24 h later and doxorubicin concentrations were measured fluorometrically. Doxorubicin concentration ratios of ipsilateral versus contralateral hemispheres were calculated, and a TEM study was performed to investigate the mechanism responsible for the increased vascular permeability induced by triolein. Results: Doxorubicin concentrations were higher in ipsilateral hemispheres at all time points, and peaked at 2 h after treatment. Doxorubicin was still detected in ipsilateral hemispheres at 24 h after treatment. TEM showed tight junction opening by triolein emulsion with lanthanum tracer spillage into neural interstitium and transcytotic vesicles. Conclusion: Doxorubicin was delivered into neural interstitium because of the increased vascular permeability of the BBB induced by triolein emulsion. Doxorubicin concentrations in brain peaked within 2 h of triolein and doxorubicin administration and remained high for 24 h. The study shows increased vascular permeability induced by triolein emulsion may involve paracellular and transcellular pathways.
Aim: The purpose of this study was to assess changes in doxorubicin concentration in rabbit brain with respect to time after BBB opening induced by triolein emulsion infusion via a carotid artery and the mechanism of BBB opening.Materials and Methods:Doxorubicin (2.4 mg/kg) was infused immediately after triolein emulsion (1%) into rabbit carotid arteries. Bilateral hemispheres were harvested 2, 4, 6 12 and 24 h later and doxorubicin concentrations were measured fluorometrically. Doxorubicin concentration ratios of ipsilateral versus contralateral hemispheres were calculated, and a TEM study was performed to investigate the mechanism responsible for the increased vascular permeability induced by triolein. Results:Doxorubicin concentrations were higher in ipsilateral hemispheres at all time points, and peaked at 2 h after treatment. Doxorubicin was still detected in ipsilateral hemispheres at 24 h after treatment. TEM showed tight junction opening by triolein emulsion with lanthanum tracer spillage into neural interstitium and transcytotic vesicles. Conclusion:Doxorubicin was delivered into neural interstitium because of the increased vascular permeability of the BBB induced by triolein emulsion. Doxorubicin concentrations in brain peaked within 2 h of triolein and doxorubicin administration and remained high for 24 h. The study shows increased vascular permeability induced by triolein emulsion may involve paracellular and transcellular pathways.