Intraarterial microbubble delivery enhances focused ultrasound induced blood brain barrier opening in the murine substantia nigra
Journal
Scientific Reports
Journal Volume
16
Journal Issue
1
Start Page
1030
ISSN
2045-2322
Date Issued
2025-11-29
Author(s)
Li, Hsun
Lee, Yung-Han
Zen, Xiao
Huang, Mei-Wei
Liu, Chia-Wei
Ho, En-Peng
Ou-Yang, Chih-Hsin
Lin, Han-I
Chen, Chih-An
Chang, Yu-Ya
Lin, Chin-Hsien
Abstract
Focused ultrasound (FUS) combined with microbubbles facilitates blood–brain barrier (BBB) opening to enhance therapeutic delivery to the substantia nigra for Parkinson’s disease treatment. While intravenous (IV) microbubble administration is commonly used, the efficacy of intra-arterial (IA) delivery remains unclear. This study compared IA versus IV administration of low (2.80 × 10⁸/kg) and high (1.12 × 10⁹/kg) microbubble doses for FUS-induced BBB opening in the murine substantia nigra. FUS was applied at a BBB-opening threshold (mechanical index: 0.42; 1 Hz; 60 s; 1% duty cycle; bregma − 3.16 mm). BBB permeability was assessed using Evans blue (EB) dye extravasation and IgG immunohistochemistry. EB staining of peripheral organs evaluated systemic off-target effects. At the low dose, Near-Infrared Fluorescence imaging on the LI-COR Odyssey system showed lower EB signals in the stomach and liver (both P = 0.01) in the IA group versus the IV low-dose MB group. Notably, high-dose IA administration led to greater IgG extravasation in deep brain regions, including thalamus (P = 0.002) and substantia nigra (P = 0.0001), and reduced off-target effects in the stomach (P = 0.004), lung (P = 0.04), liver (P = 0.004), and spleen (P = 0.02) compared to the IV high-dose group. IA delivery offers enhanced BBB opening but requires safety considerations.
Subjects
Blood-brain barrier
Focused ultrasound
Substantia nigra
Publisher
Nature Research
Type
journal article