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<p>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&#xa0;Hz; 60&#xa0;s; 1% duty cycle; bregma − 3.16&#xa0;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 <i>P</i> = 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 (<i>P</i> = 0.002) and substantia nigra (<i>P</i> = 0.0001), and reduced off-target effects in the stomach (<i>P</i> = 0.004), lung (<i>P</i> = 0.04), liver (<i>P</i> = 0.004), and spleen (<i>P</i> = 0.02) compared to the IV high-dose group. IA delivery offers enhanced BBB opening but requires safety considerations.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月29日

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  • Hsun Li,
  • Yung-Han Lee,
  • Xiao Zen,
  • Mei-Wei Huang,
  • Chia-Wei Liu,
  • En-Peng Ho,
  • Chih-Hsin Ou-Yang,
  • Han-I Lin,
  • Chih-An Chen,
  • Yu-Ya Chang,
  • Hao-Li Liu,
  • Chin-Hsien Lin

摘要

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.