Overcoming the restrictive function of the blood-brain barrier in the perifocal zone of coagulation necrosis initiated by interstitial laser hyperthermia (experimental study)

Background. The infiltrative nature of glioblastoma growth, resistance to treatment lead to its recurrent growth after standard treatment. The first-line chemotherapy has a limited effect, and after 4–8 months, most patients experience recurrent glioblastoma growth in the perifocal zone. Optimization of the penetration of existing drugs and the use of new effective drugs that do not penetrate the blood-brain barrier (BBB) is a relevant issue.

Aim. To determine the possibility of overcoming the restrictive function of the BBB when using laser hyperthermia in order to predict the possibility of glioblastoma treatment with drugs that do not penetrate the BBB.

Materials and methods. The strategy and evidence of opening the BBB in the perifocal zone of coagulation necrosis resulting from laser hyperthermia are presented. After trepanation of the skull, the dye indocyanine green (ICG) was intravenously injected into the rat’s tail vein. An optical fiber of 400 μm was inserted into the avascular area of the cortex to a depth of 2 mm, and interstitial irradiation with a wavelength of 1560 nm was performed for 50 seconds. After laser coagulation of the cortex area, the exit of ICG into the perivascular space of the perifocal zone was observed.

Results. The experiment visually demonstrated an example of extravasation of a large dye molecule, which under normal conditions does not leave the vascular bed. The observed exit of ICG into the perivascular space at the periphery of the coagulation necrosis using a fluorescent camera demonstrates the opening of the BBB.

Conclusion. The combination of cytoreductive surgery and opening of the BBB show synergistic possibilities of laser hyperthermia for chemotherapy. The emerging opportunities for using new drugs in the treatment of glioblastoma in the perifocal zone of the operated tumor are potentially able to increase the therapeutic effect and prolong the lives of patients.

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