title: Intracerebral administration of ultrasound-induced dissolution of lipid-coated GDNF microbubbles provides neuroprotection in a rat model of Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of dopaminergic neurons in the substantia nigra. Neurotrophic factors, such as glial cell derived neurotrophic factor (GDNF), have been shown to provide a neuroprotective effect in PD rats. We have previously reported that ultrasound-induced lipid-coated GDNF microspheres, which release GDNF in a sustained manner after low frequency ultrasound stimulation, can reduce hypoxic-ischemic injury in neonatal rats. In the present study, we investigated whether lipid-coated GDNF microspheres can provide a neuroprotective effect in a rat model of PD. After a rat model of PD was produced by 6-hydroxydompamine (6-OHDA) injections, lipid-coated GDNF microspheres (1.5mg/kg) were injected into the striatum of PD rats. We found that GDNF levels were increased in the striatum of PD rats after lipid-coated GDNF microspheres administration following low frequency ultrasound stimulation (20kHz, 5min per day, daily for 4 weeks). Moreover, GDNF microspheres reduced apomorphine-induced rotations, and increased striatal dopamine and nigral tyrosine hydroxylase (TH) levels in PD rats. Additionally, GDNF microspheres reduced caspase-3, tumor necrosis factor-alpha, matrix metalloproteinase 9 (MMP-9) and OX-6 levels induced by 6-OHDA injections in PD rats. These data indicated that lipid-coated GDNF microspheres can provide a neuroprotective effect in PD rats.
authors.affiliation: Department of Ultrasound, Affiliated Hospital of Xuzhou Medical College, PR China. Electronic address: xiaoyingwang2000@126.com.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, PR China.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Cui
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, PR China. Electronic address: neurologyang@126.com.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, PR China.
authors.forename: Zunsheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, PR China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zu
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000494:pharmacology; D045423:Microbubbles; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014465:Ultrasonics
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: Caspase-3; GDNF-containing microbubbles; MMP-9; OX-6; Parkinson's disease; Tumor necrosis factor-alpha