MRI-Guided Focused Ultrasound-Induced Blood Brain Barrier Disruption to Deliver Glial Cell Line Derived Neurotropic Factor Proteins into Brain to Treat Rat Depression

作者：Feng Wang, Nana Li, Xixi Wei, Xiaojian Jia, Huanhuan Liu, Yongling Wang, Yu Shi, Min Pan, Yue Wang, Yaling Yin, Fei Yan, Yun Chen · 发表于：Journal of Biomedical Nanotechnology · 年份：2020 · DOI：10.1166/jbn.2020.2914 · 被引用次数：11 · 研究领域：Ultrasound and Hyperthermia Applications、Stress Responses and Cortisol、Vagus Nerve Stimulation Research

Glial cell line derived neurotropic factor (GDNF) plays a crucial role in the development and maintenance of glial cells, serotonergic and dopaminergic neurons. A positively therapeutic effect has been demonstrated on some animal neurodegenerative diseases. However, the inability to deliver the protein across blood brain barrier (BBB) into damaged brain region limits its clinical application. Here, we developed GDNF-loaded microbubbles (MBs) and achieved a local and precise delivery of GDNF into the brain through MRI-guided focused ultrasound-induced BBB disruption. To demonstrate the therapeutic effect, rat depression model was developed by chronic mild stress treatment. Typical depression behaviors were confirmed. MRI-guided focused ultrasound was used to irradiate the GDNF-loaded MBs. Obvious BBB opening was observed in the treated rat brains and a significant higher GDNF concentration was detected in the ultrasound-treated brain tissues. Behavioral tests demonstrated the increased GDNF could reverse the depressive-like behaviors induced by chronic mild stress, improve the expression of 5-HT 1B receptor and the protein p11, and increase the number of 5-HT or TPH2 immunoreactive neurons. In conclusion, our study provided an effective approach to deliver GDNF proteins into brain to treat rat depression through MRI-guided focused ultrasound-induced destruction of blood-brain barrier.