Abstract This study aims to prepare ultrasound-targeted glial cell-derived neurotrophic factor (GDNF) retrovirus-loaded microbubbles (M pLXSN-GDNF) to verify the properties of the microbubbles and to study the therapeutic effect of the GDNF retrovirus-loaded microbubbles combined with ultrasound (U) to open the blood–brain barrier (BBB) in a Parkinson’s disease (PD) model in rats, allowing the retrovirus to pass through the BBB and transfect neurons in the substantia nigra of the midbrain, thereby increasing the expression of GDNF. The results of western blot analysis revealed significant differences between U + MpLXSN-EGFP, U + M + pLXSN-GDNF, and M pLXSN-GDNF (P < 0.05) groups. After 8 weeks of treatment, the evaluation of the effect of increased GDNF expression on behavioral deficits in PD model rats was conducted. The rotation symptom was significantly improved in the U + MpLXSN-GDNF group, and the difference before and after treatment was significant (P < 0.05). Also, the content of dopamine and the number of tyrosine hydroxylase-positive (dopaminergic) neurons were found to be higher in the brain of PD rats in the U + M pLXSN-GDNF group than in the control groups. Ultrasound combined with GDNF retrovirus-loaded microbubbles can enhance the transfection efficiency of neurons in vivo and highly express the exogenous GDNF gene to play a therapeutic role in PD model rats.

中文翻译：

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使用载有 GDNF 逆转录病毒的微泡打开血脑屏障的聚焦超声治疗帕金森病

摘要 本研究旨在制备超声靶向胶质细胞源性神经营养因子（GDNF）逆转录病毒微泡（M pLXSN-GDNF），以验证微泡的性质并研究GDNF逆转录病毒微泡与逆转录病毒微泡结合的治疗效果。超声（U）在大鼠帕金森病（PD）模型中打开血脑屏障（BBB），使逆转录病毒通过血脑屏障并转染中脑黑质中的神经元，从而增加 GDNF 的表达. 蛋白质印迹分析结果显示，U + MpLXSN-EGFP、U + M + pLXSN-GDNF 和 M pLXSN-GDNF 组之间存在显着差异（P < 0.05）。治疗8周后，评估GDNF表达增加对PD模型大鼠行为缺陷的影响。U+MpLXSN-GDNF组旋转症状明显改善，治疗前后差异有显着性（P<0.05）。此外，U+M pLXSN-GDNF组PD大鼠脑中多巴胺含量和酪氨酸羟化酶阳性（多巴胺能）神经元数量高于对照组。超声结合载有GDNF逆转录病毒的微泡可提高体内神经元的转染效率，并高表达外源性GDNF基因，对PD模型大鼠起到治疗作用。发现U+M pLXSN-GDNF组PD大鼠脑中多巴胺含量和酪氨酸羟化酶阳性（多巴胺能）神经元数量高于对照组。超声结合载有GDNF逆转录病毒的微泡可提高体内神经元的转染效率，并高表达外源性GDNF基因，对PD模型大鼠起到治疗作用。发现U+M pLXSN-GDNF组PD大鼠脑中多巴胺含量和酪氨酸羟化酶阳性（多巴胺能）神经元数量高于对照组。超声结合载有GDNF逆转录病毒的微泡可提高体内神经元的转染效率，并高表达外源性GDNF基因，对PD模型大鼠起到治疗作用。