Stefani Alessandro, Pierantozzi Mariangela, Cardarelli Silvia, Stefani Lucrezia, Cerroni Rocco, Conti Matteo, Garasto Elena, Mercuri Nicola B, Marini Carmine, Sucapane Patrizia
Department of System Medicine, Parkinson Center, University Tor Vergata, Rome, Italy.
Department of System Medicine, UOC Neurology, University Tor Vergata, Rome, Italy.
Front Neurosci. 2022 Mar 25;16:846681. doi: 10.3389/fnins.2022.846681. eCollection 2022.
Magnetic Resonance-guided Focused Ultrasound (MRgFUS) represents an effective micro-lesioning approach to target pharmaco-resistant tremor, mostly in patients afflicted by essential tremor (ET) and/or Parkinson's disease (PD). So far, experimental protocols are verifying the clinical extension to other facets of the movement disorder galaxy (i.e., internal pallidus for disabling dyskinesias). Aside from those neurosurgical options, one of the most intriguing opportunities of this technique relies on its capability to remedy the impermeability of blood-brain barrier (BBB). Temporary BBB opening through low-intensity focused ultrasound turned out to be safe and feasible in patients with PD, Alzheimer's disease, and amyotrophic lateral sclerosis. As a mere consequence of the procedures, some groups described even reversible but significant mild cognitive amelioration, up to hippocampal neurogenesis partially associated to the increased of endogenous brain-derived neurotrophic factor (BDNF). A further development elevates MRgFUS to the status of therapeutic tool for drug delivery of putative neurorestorative therapies. Since 2012, FUS-assisted intravenous administration of BDNF or neurturin allowed hippocampal or striatal delivery. Experimental studies emphasized synergistic modalities. In a rodent model for Huntington's disease, engineered liposomes can carry glial cell line-derived neurotrophic factor (GDNF) plasmid DNA (GDNFp) to form a GDNFp-liposome (GDNFp-LPs) complex through pulsed FUS exposures with microbubbles; in a subacute MPTP-PD model, the combination of intravenous administration of neurotrophic factors (either through protein or gene delivery) plus FUS did curb nigrostriatal degeneration. Here, we explore these arguments, focusing on the current, translational application of neurotrophins in neurodegenerative diseases.
磁共振引导聚焦超声（MRgFUS）是一种针对药物难治性震颤的有效微损伤治疗方法，主要用于患有特发性震颤（ET）和/或帕金森病（PD）的患者。到目前为止，实验方案正在验证该技术在运动障碍领域其他方面的临床应用扩展（例如，用于治疗致残性运动障碍的内侧苍白球）。除了这些神经外科手术选择外，这项技术最吸引人的机会之一在于其修复血脑屏障（BBB）通透性的能力。在帕金森病、阿尔茨海默病和肌萎缩侧索硬化症患者中，通过低强度聚焦超声暂时打开血脑屏障被证明是安全可行的。作为这些操作的一个结果，一些研究小组甚至描述了可逆但显著的轻度认知改善，甚至部分与内源性脑源性神经营养因子（BDNF）增加相关的海马神经发生。进一步的发展将MRgFUS提升为用于推定神经修复疗法药物递送的治疗工具。自2012年以来，聚焦超声辅助静脉注射BDNF或神经营养素，实现了海马或纹状体递送。实验研究强调了协同模式。在亨廷顿舞蹈病的啮齿动物模型中，工程化脂质体可以携带胶质细胞源性神经营养因子（GDNF）质粒DNA（GDNFp），通过与微泡的脉冲聚焦超声照射形成GDNFp-脂质体（GDNFp-LPs）复合物；在亚急性MPTP-PD模型中，静脉注射神经营养因子（通过蛋白质或基因递送）加聚焦超声的联合应用确实抑制了黑质纹状体变性。在此，我们探讨这些问题，重点关注神经营养因子在神经退行性疾病中的当前转化应用。
