Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma

低强度激光治疗诱导血脑屏障开放和脑排水系统激活:将脂质体输送到小鼠胶质母细胞瘤中

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作者:Oxana Semyachkina-Glushkovskaya, Denis Bragin, Olga Bragina, Sergey Socolovski, Alexander Shirokov, Ivan Fedosov, Vasily Ageev, Inna Blokhina, Alexander Dubrovsky, Valeria Telnova, Andrey Terskov, Alexander Khorovodov, Daria Elovenko, Arina Evsukova, Maria Zhoy, Ilana Agranovich, Elena Vodovozova, A

Abstract

The progress in brain diseases treatment is limited by the blood-brain barrier (BBB), which prevents delivery of the vast majority of drugs from the blood into the brain. In this study, we discover unknown phenomenon of opening of the BBBB (BBBO) by low-level laser treatment (LLLT, 1268 nm) in the mouse cortex. LLLT-BBBO is accompanied by activation of the brain drainage system contributing effective delivery of liposomes into glioblastoma (GBM). The LLLT induces the generation of singlet oxygen without photosensitizers (PSs) in the blood endothelial cells and astrocytes, which can be a trigger mechanism of BBBO. LLLT-BBBO causes activation of the ABC-transport system with a temporal decrease in the expression of tight junction proteins. The BBB recovery is accompanied by activation of neuronal metabolic activity and stabilization of the BBB permeability. LLLT-BBBO can be used as a new opportunity of interstitial PS-free photodynamic therapy (PDT) for modulation of brain tumor immunity and improvement of immuno-therapy for GBM in infants in whom PDT with PSs, radio- and chemotherapy are strongly limited, as well as in adults with a high allergic reaction to PSs.

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