Effects of focused ultrasound sonodynamic treatment on the rat blood-brain barrier.
BACKGROUND
Ultrasound has recently been applied to the treatment as well as the diagnosis of various pathologies, and its antitumor effects in the treatment of human cancer and experimental models of cancer have been demonstrated. In addition, it is possible that certain photosensitizers will enhance the antitumor effects of ultrasound. However, very few studies have been reported on how the blood-brain barrier is affected by sonodynamic therapy. The purpose of this study was to evaluate disruption of the blood-brain barrier with focused ultrasound with a photosensitizer, for clinical application of sonodynamic therapy to brain tumors.


METHODS
Rat brains were subjected to focused ultrasound irradiation via a transducer with or without prior intravenous injection of photosensitizer, and lesions were examined histologically by electron microscopy.


RESULTS
Electron microscopically, swelling of astroglial processes, denatured cells, protoplasm of endothelial cells, and mitochondria were observed in the center and border of regions of ultrasonic irradiation. There were numerous pinocytotic vesicles in the cytoplasm of the endothelial cells. In addition, disruption of the cytoplasmic membrane of endothelial cells and astroglia was found in these regions.


CONCLUSIONS
These findings suggest that sonodynamic therapy with a photosensitizer affects the blood-brain barrier, and that blood vessel permeability increases not only as a result of destruction of the blood-brain barrier but also by disruption of the cytoplasmic membrane of endothelial cells.
Department of Neurosurgery, Fukuoka University Faculty of Medicine, Hakata-ku, Fukuoka 812-0046, Japan. yoshino.s02@city.fukuoka.jp
Shin-Ichiro
S
Yoshino
Takeo
T
Fukushima
Shuji
S
Hayashi
Masani
M
Nonaka
Kohichi
K
Ogawa
Kazunari
K
Sasaki
Shin-Ichiro
S
Umemura
D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005260:Female; D008928:Mitochondria / Q000648:ultrastructure; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012395:Rose Bengal / Q000627:therapeutic use*; D014464:Ultrasonic Therapy; D014463:Ultrasonography
D017319:Photosensitizing Agents; D012395:Rose Bengal