Treatment of Parkinson's disease in rats by Nrf2 transfection using MRI-guided focused ultrasound delivery of nanomicrobubbles.
Parkinson's disease (PD) is a very common neurological disorder. However, effective therapy is lacking. Although the blood-brain-barrier (BBB) protects the brain, it prevents the delivery of about 90% of drugs and nucleotides into the brain, thereby hindering the development of gene therapy for PD. Magnetic resonance imaging (MRI)-guided focused ultrasound delivery of microbubbles enhances the delivery of gene therapy vectors across the BBB and improves transfection efficiency. In the present study, we delivered nuclear factor E2-related factor 2 (Nrf2, NFE2L2) contained in nanomicrobubbles into the substantia nigra of PD rats by MRI-guided focused ultrasound, and we examined the effect of Nrf2 over-expression in this animal model of PD. The rat model of PD was established by injecting 6-OHDA in the right substantia nigra stereotactically. Plasmids (pDC315 or pDC315/Nrf2) were loaded onto nanomicrobubbles, and then injected through the tail vein with the assistance of MRI-guided focused ultrasound. MRI-guided focused ultrasound delivery of nanomicrobubbles increased gene transfection efficiency. Furthermore, Nrf2 gene transfection reduced reactive oxygen species levels, thereby protecting neurons in the target region.
Department of Neurology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Ling
L
Long
Department of Neurology, Sixth Affiliated Hospital, Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital), Guangzhou, China.
Xiaodong
X
Cai
Department of Radiology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Ruomi
R
Guo
Department of Ultrasonics, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Ping
P
Wang
Department of Ultrasonics, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Lili
L
Wu
Department of Ultrasonics, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Tinghui
T
Yin
Department of Neurology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Siyuan
S
Liao
Department of Neurology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address: lzq1828@163.com.
Zhengqi
Z
Lu
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D005260:Female; D015316:Genetic Therapy; D053783:Magnetic Resonance Imaging, Interventional; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013010:Sonication; D014018:Tissue Distribution; D014162:Transfection; D016896:Treatment Outcome
D002214:Capsules; D051267:NF-E2-Related Factor 2; D053769:Nanocapsules; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species
Blood-brain-barrier (BBB); MRI-Guided focused ultrasound nanomicrobubble; Nuclear factor E2-related factor 2 (Nrf2); Parkinson's disease (PD); Reactive oxygen species (ROS)