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. 2025 Nov 29.
doi: 10.1038/s41598-025-30757-0. Online ahead of print.

Intraarterial microbubble delivery enhances focused ultrasound induced blood brain barrier opening in the murine substantia nigra

Hsun Li #  1 , Yung-Han Lee #  2 , Xiao Zen  3 , Mei-Wei Huang  2 , Chia-Wei Liu  1 , En-Peng Ho  1 , Chih-Hsin Ou-Yang  1 , Han-I Lin  1 , Chih-An Chen  4 , Yu-Ya Chang  4 , Hao-Li Liu  5   6   7 , Chin-Hsien Lin  8   9   10   11   12
Affiliations
Free article

Intraarterial microbubble delivery enhances focused ultrasound induced blood brain barrier opening in the murine substantia nigra

Hsun Li et al. Sci Rep. .
Free article

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.

Keywords: Blood-brain barrier; Focused ultrasound; Substantia nigra.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics declarations: All animal experiments were approved by the Institutional Animal Care and Use Committee of the National Taiwan University Hospital (IACUC 20210059) and were conducted in accordance with the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines.

References

    1. Hynynen, K. Ultrasound for drug and gene delivery to the brain. Adv. Drug Deliv Rev. 60, 1209–1217 (2008).
    1. Yao, H. et al. Enhanced blood-brain barrier penetration and glioma therapy mediated by a new peptide modified gene delivery system. Biomaterials 37, 345–352 (2015).
    1. McMahon, D., Poon, C. & Hynynen, K. Evaluating the safety profile of focused ultrasound and microbubble-mediated treatments to increase blood-brain barrier permeability. Expert Opin. Drug Deliv. 16, 129–142 (2019).
    1. Meng, Y. et al. MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases. Sci. Transl Med. 13, eabj4011 (2021).
    1. Baseri, B. et al. Activation of signaling pathways following localized delivery of systemically administered neurotrophic factors across the blood-brain barrier using focused ultrasound and microbubbles. Phys. Med. Biol. 57, N65–81 (2012).

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