Targeting the endocannabinoid system: a predictive, preventive, and personalized medicine-directed approach to the management of brain pathologies.

Cannabis-inspired medical products are garnering increasing attention from the scientific community, general public, and health policy makers. A plethora of scientific literature demonstrates intricate engagement of the endocannabinoid system with human immunology, psychology, developmental processes, neuronal plasticity, signal transduction, and metabolic regulation. Despite the therapeutic potential, the adverse psychoactive effects and historical stigma, cannabinoids have limited widespread clinical application. Therefore, it is plausible to weigh carefully the beneficial effects of cannabinoids against the potential adverse impacts for every individual. This is where the concept of "personalized medicine" as a promising approach for disease prediction and prevention may take into the account. The goal of this review is to provide an outline of the endocannabinoid system, including endocannabinoid metabolizing pathways, and will progress to a more in-depth discussion of the therapeutic interventions by endocannabinoids in various neurological disorders.

Effect of plasma-derived extracellular vesicles on erythrocyte deformability in polymicrobial sepsis.

Sepsis affects microcirculation and tissue perfusion leading to tissue hypoxia and multiple organ dysfunction. Red blood cells (RBCs; erythrocytes) are typically biconcave in shape, transport hemoglobin-bound oxygen and are reversibly deformable facilitating trafficking through capillaries. Decreased deformability of RBCs adversely affects tissue oxygenation. The purpose of this project was to determine RBC deformability in a murine model of polymicrobial sepsis by a method that utilizes laser diffraction and microfluidics, and to identify the causative factors in the plasma that may contribute to loss in RBC deformability. Blood samples from mice subjected to cecal ligation and puncture (CLP) model of sepsis were used. RBC deformability was tested using Rheoscan-AnD 300 under shear stress range of 0-20 Pascal (Pa) that depicts the common rheological behavior of RBCs flowing through blood vessels ranging from major vessels to capillaries. Normal RBCs were treated with plasma-derived extracellular vesicles (EVs) and their effect on RBC deformability was also tested. The experiments demonstrated a significant decrease in RBC deformability following sepsis. RBC deformability recovered in sham-operated animals by the third day, whereas animals with sepsis continued to show decreased levels of deformability. EVs isolated from the plasma of animals from the sepsis group significantly decreased deformability of RBCs ex vivo. Analysis of miRNA cargo in EVs showed distinct molecular profiles for sham-operated and sepsis-induced mice. In summary, sepsis induced a decrease in RBC deformability and the acquired rigidity may have adverse effect on microcirculation, tissue perfusion, and organ function.