期刊
ULTRASOUND IN MEDICINE AND BIOLOGY
卷 38, 期 7, 页码 1234-1243出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2012.02.019
关键词
Blood-brain barrier; Central nervous system; Gene therapy; Ultrasound; Microbubbles
资金
- National Natural Science Foundation of China [30870723]
- Chongqing Natural Science Foundation [CSTC, 2008BB5234]
To investigate whether ultrasound-targeted microbubble destruction (UTMD) could transfer gene into central nervous system (CNS) following blood-brain barrier disruption (BBBD), DNA-loaded microbubbles were infused into the mice intravenously following ultrasonic exposure. Opening of the BBB, changes of mRNA and expression of enhanced green fluorescent protein (EGFP), and safety evaluation were measured. By UTMD, EGFP were substantially expressed in the cytoplasm of the neurons at the sonicated area with minor erythrocytes extravasation and the mRNA and expression of EGFP were markedly enhanced by about 15-fold and 10-fold, respectively, than that with US alone (p < 0.01). No EGFP was detected in the mice treated with DNA-loaded microbubbles or plasmid alone. The gene expression reached a climax at 48 h, gradually reduced to a much lower level thereafter. These results demonstrated UTMD could effectively enhance exogenous gene delivery and expression in CNS following BBBD, and this technique may provide a new method for CNS gene therapy. (E-mail: chengyuan023@yahoo.com.cn) (C) 2012 World Federation for Ultrasound in Medicine & Biology.
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