Nigrostriatal blood-brain barrier opening in Parkinson's disease.

IF 8.7 1区医学 Q1 CLINICAL NEUROLOGY Journal of Neurology, Neurosurgery, and Psychiatry Pub Date : 2024-10-16 DOI:10.1136/jnnp-2023-332967

Carmen Gasca-Salas, José A Pineda-Pardo, Marta Del Álamo, Tamara Jiménez, Clara Trompeta, Gabriella Toltsis, Lina Garcia-Cañamaque, Beatriz Fernández-Rodríguez, Michele Matarazzo, Isabel Plaza de Las Heras, Elena Natera-Villalba, Raúl Martínez-Fernández, Alicia Duque, Santiago Ruiz de Aguiar, Javier Blesa, Itay Rachmilevich, José A Obeso

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Abstract

Background: The nigrostriatal system is especially vulnerable to neurodegeneration in Parkinson's disease (PD) and the blood-brain barrier (BBB) is a limiting factor for delivery of therapeutic agents to the brain. This pilot study aimed to demonstrate safety, feasibility and tissue penetration (by 18F-Choline-positron emission tomography (PET)) of MR-guided focused ultrasound (MRgFUS) simultaneous BBB opening (BBB-O) in the substantia nigra (SN) and putamen in PD.

Methods: Three patients underwent MRgFUS for midbrain and putamen BBB-O. Patients were evaluated clinically and underwent brain MRI with gadolinium (baseline, 24 hours, 14 days and 3 months postprocedure). In two patients, BBB-O was repeated after 2-3 weeks, and 18F-Choline-PET was performed immediately after.

Results: The right SN and putamen were simultaneously opened unilaterally in 3 patients once and the left SN in 1 patient in a different session. No severe clinical or neuroimaging adverse events developed in any patient. 18F-Choline-PET uptake was enhanced in the targeted SN and putamen regions.

Conclusion: BBB-O of the nigrostriatal system is a feasible and well-tolerated approach in patients with PD. 18F-Choline-PET uptake indicates penetration into the parenchyma after BBB-O, which suggests that the opening is functionally effective. This minimally invasive technique could facilitate delivery of putative neurorestorative molecules to brain regions vulnerable to neurodegeneration.

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帕金森病的黑质纹状体血脑屏障开放。

背景：帕金森病（PD）的黑质纹状体系统特别容易发生神经变性，而血脑屏障（BBB）是将治疗药物输送到大脑的一个限制因素。这项试验性研究旨在证明磁共振引导下聚焦超声（MRgFUS）在帕金森病黑质（SN）和柱状体同时打开（BBB-O）的安全性、可行性和组织穿透性（通过18F-胆碱正电子发射断层扫描（PET））：三名患者接受了MRgFUS治疗中脑和柱状体BBB-O。对患者进行了临床评估，并用钆进行了脑磁共振成像（基线、术后24小时、14天和3个月）。两名患者在 2-3 周后再次进行了 BBB-O 检查，并在检查后立即进行了 18F-Choline-PET 检查：结果：3 名患者同时单侧打开了右侧神经元和普鲁卡因，1 名患者在另一次手术中同时打开了左侧神经元。所有患者均未出现严重的临床或神经影像不良反应。18F-胆碱-PET摄取在目标SN和普鲁曼区域增强：结论：黑质纹状体系统的BBB-O是一种可行且耐受性良好的方法，适用于帕金森病患者。18F-胆碱-PET摄取表明，BBB-O后可渗透至实质组织，这表明BBB-O在功能上是有效的。这种微创技术有助于向易受神经变性影响的大脑区域输送具有神经恢复功能的分子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Neurology, Neurosurgery, and Psychiatry 医学-精神病学

CiteScore

15.70

自引率

1.80%

发文量

888

审稿时长

6 months

期刊介绍： The Journal of Neurology, Neurosurgery & Psychiatry (JNNP) aspires to publish groundbreaking and cutting-edge research worldwide. Covering the entire spectrum of neurological sciences, the journal focuses on common disorders like stroke, multiple sclerosis, Parkinson’s disease, epilepsy, peripheral neuropathy, subarachnoid haemorrhage, and neuropsychiatry, while also addressing complex challenges such as ALS. With early online publication, regular podcasts, and an extensive archive collection boasting the longest half-life in clinical neuroscience journals, JNNP aims to be a trailblazer in the field.