Scientists have found that low doses of methamphetamine caseolaris facilitate the transport of other substances across the blood-brain barrier. Apply it to as small molecules and proteins, and therefore, methamphetamine may become a universal auxiliary substance for drug delivery to the Central nervous system. The authors of the article, a Preprint of which is available on the portal bioRxiv, tested the methamphetamine as a complement to chemotherapy for the treatment of glioblastoma model in mice, and the animals lived longer.
Central nervous system is separated from the blood vessels of the blood-brain barrier, which does not penetrate into the brain “foreign” substances. What to put and what not to put, decide endothelial cells, which form a physical barrier, and to deliver drugs into the brain, scientists are trying to deceive them.
One of the proposed ways to “push” drugs through the blood-brain barrier with the aid of methamphetamine. It is a narcotic substance in a concentration more than ten micromole per liter violates (sometimes permanently) tight contacts between endothelial cells and barrier appear in the gaps. In small doses, methamphetamine also increases the conductivity of the blood brain barrier, but not physically violating him, enhancing vesicular transport of fluids through the cell wall.
Scientists from the UK and Ireland under the leadership of Patrick Turovsky (Patric Turowski) from University College London studied the mechanism of action of methamphetamine on the blood-brain barrier. This created a model of ex vivo perfusion of the brain of rodents in the carotid artery of the animals immediately after death, inserted catheters, and jugular vein cut. The catheters through the brain passed a solution that preserves the integrity of the vasculature and the blood brain barrier. In the solution, which is injected through one of the catheters, added meth, and the second served as a control.
For a start, convinced of the integrity of the blood-brain barrier — it is in the carotid artery of rats was injected the dye, which normally does not pass through the barrier. Then one of the two solutions added methamphetamine at a concentration of one micromole per liter. After 60 minutes vascular network washed, so that the dye remained only where it passed through the blood-brain barrier.
In the hemisphere, through which passed a solution of meth the dye passed through the barrier and accumulated in the brain, and in the second (control) hemisphere that did not happen. Using electron microscopy found that the processes of astrocytes after exposure to methamphetamine increased in size and compressed capillaries. Tight contacts between endothelial cells was preserved, and the dye did not accumulate in them, but inside of these cells had many vesicles with the dye.