Abstract

Photodynamic treatment (PDT) causes a significant increase in the permeability of the blood-brain barrier (BBB) in healthy mice. Using different doses of laser radiation (635 nm, 10-40 J/cm2) and photosensitizer (5-aminolevulinic acid - 5-ALA, 20 and 80 mg/kg, i.v.), we found that the optimal PDT for the reversible opening of the BBB is 15 J/cm2 and 5-ALA, 20 mg/kg, exhibiting brain tissues recovery 3 days after PDT. Further increases in the laser radiation or 5-ALA doses have no amplifying effect on the BBB permeability, but are associated with severe damage of brain tissues. These results can be an informative platform for further studies of new strategies in brain drug delivery and for better understanding of mechanisms underlying cerebrovascular effects of PDT-related fluorescence guided resection of brain tumor.

Highlights

  • The blood-brain barrier (BBB) is a gatekeeper located on the endothelial cells of the microvasculature and controls the passage of blood-borne agents into the brain tissues playing an important role for the health of the central nervous system

  • Using different doses of laser radiation (635 nm, 10-40 J/cm2) and photosensitizer (5-aminolevulinic acid – 5-aminole-vulinic acid (5-ALA), 20 and 80 mg/kg, i.v.), we found that the optimal Photodynamic treatment (PDT) for the reversible opening of the BBB is 15 J/cm2 and 5ALA, 20 mg/kg, exhibiting brain tissues recovery 3 days after PDT

  • PDT- induced BBB disruption evaluated by assessment of Evans Blue dye (EBd) leakage

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Summary

Introduction

The blood-brain barrier (BBB) is a gatekeeper located on the endothelial cells of the microvasculature and controls the passage of blood-borne agents into the brain tissues playing an important role for the health of the central nervous system. These protective mechanisms restrict the entrance of many drugs into the brain. There are 7000 drugs, which are registered in the Comprehensive Medicinal Chemistry database but only 5% of them are available to treat the neuronal diseases because antibodies, recombinant proteins, therapeutic genes and most small molecules cannot penetrate the BBB [1, 2]. No methods are developed yet, which are widely used in daily clinical practice for the opening of the BBB due to their invasiveness and challenging nature [6,7,8]

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