Cite this article as:

Semyachkina-Glushkovskaya O. V., Shirokov A. A., Novolokin N. A., Terskov A. V., Bodrova A. A., Shushunova N. A., Khorovodov A. P., Ulanova M. V., Agranovich I. M., Iskra T. D., Mamedova A. T. Optimization of Photodynamic Effects on Permeability of Cerebral Vessels. Izvestiya of Saratov University. Chemistry. Biology. Ecology, 2018, vol. 18, iss. 4, pp. 423-428. DOI:

This is an open access article distributed under the terms of Creative Commons Attribution 4.0 International License (CC-BY 4.0).

Optimization of Photodynamic Effects on Permeability of Cerebral Vessels


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, i.v.), we found the optimal PDT for the reversible opening of the BBB, exhibiting brain tissue 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 resection of brain tumor.


1. Abbott N. J., Patabendige A. A., Dolman D. E., Yusof S. R., Begley D. J. Structure and function of the blood-brain barrier // J. Neurobiol Dis. 2010. Vol. 37, № 1. P. 13–25.

2. Pardridge W. M. Blood-brain barrier delivery // Journal Drug Discov. Today. 2007. Vol. 12, № 1–2. P. 54–61.

3. Mizutani T. A., Murayama Y., Ikoma H., Arita T., Kosuga T., Konishi H., Morimura R., Shiozaki A., Kuriu Y., Nakanishi M., Fujiwara H., Okamoto K., Otsuji E. Useful Case of Photodynamic Diagnosis of Inferior Vena Cava Invasion by Pancreatic Head Cancer Using 5-Aminolevulinic Acid (5-ALA) // Gan to Kagaku Ryoho. 2018. Vol. 45, № 3. P. 575–577.

4. Stummer W., Stepp H., Wiestler O. D., Pichlmeier U. Randomized, Prospective Double-Blinded Study Comparing 3 Different Doses of 5-Aminolevulinic Acid for Fluorescence-Guided Resection of Malignant Gliomas // Neurosurgery. 2017. Vol. 81, № 2. P. 230–239.

5. Kuroiwa T. Photodynamic diagnosis and photodynamic therapy for the brain tumors // Progress in Neuro-Oncology. 2014. Vol. 21, № 3. P. 14–21.

6. Krammer B. Vascular effects of photodynamic therapy // Anticancer Res. 2001. Vol. 21, № 6B. P. 4271–4277.

7. Stylli S. S., Kaye A. H. Photodynamic therapy of cerebral glioma-A review Part I-A biological basis // J. Clin. Neurosci. 2006. Vol. 13, № 6. P. 615–625.

8. Hirschberg H., Uzal F. A., Chighvinadze D., Zhang M. J., Peng Q., Madsen S. J. Disruption of the B lood-Brain Barrier Following ALA-Mediated Photodynamic Therapy // Lasers Surg. Med. 2008. Vol. 40, № 8. P. 535–542.

9. Madsen, S. J., Gach H. M., Hong S. J., Uzal F. A., Peng Q., Hirschberg H. Increased nanoparticle-loaded exogenous macrophage migration into the brain following PDT-induced blood-brain barrier disruption // Lasers Surg. Med. 2013. Vol. 45, № 8. P. 524–532.

10. Hoffmann A., Bredno J., Wendland M., Derugin N., Ohara P., Wintermark M. High and low molecular weight fl uorescein isothiocyanate (FITC)-dextran to assess blood-brain barrier disruption : technical consideration // Transl. Stroke Res. 2011. Vol. 2, № 1. P. 106–111.

11. Semyachkina-Glushkovskaya O., Abdurashitov A., Pavlov A., Shirokov A., Navolokin N., Pavlova O., Gekalyuk A., Ulanova M., Shushunova N., Bodrova A., Saranceva E., Khorovodov A., Agranovich I., Fedorova V., Sagatova M., Shareef A. E., Zhang C., Zhu D., Tuchin V. Laser speckle imaging and wavelet analysis of cerebral blood fl ow associated with the opening of the blood–brain barrier by sound // Chin. Opt. Lett. 2017. Vol. 15, № 9. P. 090002.

12. Angell-Petersen E., Spetalen S., Madsen S. J., Sun C. H., Peng Q., Carper S. W., Sioud M., Hirschberg H. Infl uence of light fl uence rate on the effects of photodynamic therapy in an orthotopic rat glioma model // J. Neurosurg. 2006. Vol. 104, № 1. P. 109–117.

Short text (in English): 
Full text (in Russian):