Age differences in photodynamic therapy-mediated opening of the blood-brain barrier through the optical clearing skull window in mice

Lasers in Surgery and Medicine
Chao ZhangDan Zhu

Abstract

Photodynamic therapy (PDT), a minimally invasive therapeutic tool, has been an important option for post-surgical treatment of malignant gliomas (MGs) in both adult and young patients. Recent studies have shown that PDT can also open the blood-brain barrier (BBB). However, there are no optimized parameters of PDT for patients at different ages. To determine whether there are age differences in PDT effects on the BBB, we studied PDT-related BBB opening through the optical clearing skull window in healthy 4- and 8-week-old mice. In this work, we realized BBB opening by combining PDT with the optical clearing skull window by using different radiant exposures (635 nm, 10-20-30-40 J/cm2 ) and 5-aminole-vulinic acid (5-ALA, 20 mg/kg). Then, we evaluated BBB permeability by: (i) spectrofluorimetric measuring of Evans Blue dye (EBd) leakage; (ii) confocal imaging of 70 kDa FITC-dextran extravasation and the BBB integrity; and (iii) histological analysis of brain tissues. Using the skull optical clearing method, we demonstrated PDT-induced BBB opening to EBd and FITC-dextran in a radiant exposure manner. The histological analysis revealed the different severities of vasogenic edema corresponding to radiant exposures. Besides, the PDT-re...Continue Reading

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Dec 29, 2020·Journal of Neuroscience Research·Luis Exequiel IbarraLaura Natalia Milla Sanabria

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