Abstract
Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), are promising therapeutic agents for neurodegenerative diseases. However, the application of GDNF to treat these diseases effectively is limited because the blood–brain barrier (BBB) prevents the local delivery of macromolecular therapeutic agents from entering the central nervous system (CNS). Focused ultrasound combined with microbubbles (MBs) using appropriate parameters has been previously demonstrated to be able to open the BBB locally and noninvasively. This study investigated the targeted delivery of GDNF MBs through the BBB by magnetic resonance imaging (MRI)-guided focused ultrasound. Evans Blue extravasation and histological examination were used to determine the optimum focused ultrasound parameters. Enzyme-linked immunosorbent assay was performed to verify the effects of GDNF bound on MBs using a biotin–avidin bridging chemistry method to promote GDNF delivery into the brain. The results showed that GDNF can be delivered locally and noninvasively into the CNS through the BBB using MRI-guided focused ultrasound combined with MBs under optimum parameters. MBs that bind GDNF combined with MRI-guided focused ultrasound may be an effective way of delivering neurotrophic factors directly into the CNS. The method described herein provides a potential means of treating patients with CNS diseases.
Highlights
Neurotrophic factors have emerged as promising tools for the treatment of various neurodegenerative diseases
Increased glial cell line-derived neurotrophic factor (GDNF) levels in the central nervous system (CNS) may be beneficial to the treatment of neurodegenerative diseases, such as Parkinson’s disease (PD) and drug addiction [5,6], the therapeutic application of GDNF is limited because efficient methods of delivering it to the CNS are currently not available
Of the neurotrophic factors currently available, GDNF has proven to be remarkably effective in controlling PD and drug addiction [10,18]
Summary
Neurotrophic factors have emerged as promising tools for the treatment of various neurodegenerative diseases. GDNF is an essential growth factor for the development of the kidneys and spinal cord motoneurons, and it exerts a wide range of effects on peripheral and central neurons [2]. Several studies have suggested that GDNF is a potential target in the treatment of drug addiction. Increased GDNF levels in the central nervous system (CNS) may be beneficial to the treatment of neurodegenerative diseases, such as PD and drug addiction [5,6], the therapeutic application of GDNF is limited because efficient methods of delivering it to the CNS are currently not available
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