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The unloaded PEGylated liposomes\u2010coupled microbubbles (PLs\u2010MBs) were characterized for zeta potential, particle size, and concentration. 6\u2010hydroxydopamine (6\u2010OHDA) was used to establish the PD rat model. Rotational, climbing pole, and suspension tests were used to detect behavioral impairment. The immunohistochemical staining of tyrosine hydroxylase (TH) and dopamine transporter (DAT) was used to assess the neuron loss. Western blot and quantitative real\u2010time PCR (qRT\u2010PCR) analysis were used to measure the expression levels of GDNF and Nurr1. The particle size of PLs\u2010MBs was gradually increased, while the concentration and absolute zeta potential were gradually decreased as the time prolongs. 6\u2010OHDA increased amphetamine\u2010induced rotations and loss of dopaminergic neurons as compared to sham group. Interestingly, PLs\u2010GDNF\u2010MBs or PLs\u2010Nurr1\u2010MBs decreased rotations and increased the TH and DAT immunoreactivity. Combined of both genes resulted in a robust reduction in the rotations and a greater increase of the dopaminergic neurons. The delivery of PLs\u2010GDNF\u2009+\u2009Nurr1\u2010MBs into the brains using magnetic resonance imaging (MRI)\u2010guided focused ultrasound may be more efficacious for the treatment of PD than the single treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.26608","type":"journal-article","created":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T14:29:06Z","timestamp":1513261746000},"page":"4581-4591","source":"Crossref","is-referenced-by-count":31,"title":["Ultrasound\u2010triggered effects of the microbubbles coupled to GDNF\u2010 and Nurr1\u2010loaded PEGylated liposomes in a rat model of Parkinson's disease"],"prefix":"10.1002","volume":"119","author":[{"given":"Peijian","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurological Intensive Care Unit The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-6131","authenticated-orcid":false,"given":"Junfang","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026045"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10447"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/ern.11.203"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2012.12.022"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.11.038"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-0618(01)00115-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)03217-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.169"},{"key":"e_1_2_7_10_1","first-page":"10","article-title":"GDNF\u2010based therapies, GDNF\u2010producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. 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