MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles.

Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood-brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.

Finger beat-to-beat blood pressure responses to successive hand elevations.

We investigated finger beat-to-beat blood pressure responses to a series of successive hand elevations in 14 normal volunteers. By passive elevation of the hand by 40 cm and lowering it again after a minute, calibrated hydrostatic pressure changes were induced in the finger arteries of the subjects. Three successive procedures with a 2-min interval between them were performed. Transitions between positions were completed smoothly over a 10-s period. Non-invasive beat-to-beat mean arterial pressure (MAP) in the finger arteries was measured by applying the servo-oscillometric physiograph (University of Tartu, Estonia). A good agreement between the evoked MAP changes during all the three hand elevations (-31.2, -30.4 and -30.0 mmHg, respectively) and the calculated hydrostatic pressure change (-31.0 mmHg) was obtained. The height difference of approximately 40 cm and rate of 4-5 cm/s can be recommended for the hand elevation test, greater postural changes and higher rates may diminish agreement between the measured blood pressure response and the corresponding hydrostatic pressure change. The applied hydrostatic test may be helpful for assessing the accuracy of beat-to-beat finger blood pressure measurement.