Leukocyte rolling on the vascular endothelium requires initial contact between leukocytes circulating in the blood and the vessel wall. Although specific adhesion mechanisms are involved in leukocyte-endothelium interactions, adhesion patterns in vivo suggest other rheological mechanisms also play a role. Previous studies have proposed that the abundance of leukocyte rolling in postcapillary venules is due to interactions between red blood cells (RBCs) and leukocytes as they enter postcapillary expansions, but the details of the fluid dynamics have not been elucidated. We have analyzed the interactions of red and white blood cells as they flow from a capillary into a postcapillary venule using a lattice Boltzmann approach. This technique provides the complete solution of the flow field and quantification of the particle-particle forces in a relevant geometry. Our results show that capillary-postcapillary venule diameter ratio, RBC configuration, and RBC shape are critical determinants of the initiation of cell rolling in postcapillary venules. The model predicts that an optimal configuration of the trailing red blood cells is required to drive the white blood cell to the wall.

BackgroundOur previous study found that suppression of TRPM7 reduced neuronal death in adult rat ischemic brain injury. It was reported that carvacrol blocked TRPM7 and attenuated brain injury in an adult rat MCAO model. The effects of carvacrol on neonatal stroke remain unknown. This study investigated the effects of carvacrol on neuronal injury and behavioral impairment after hypoxia-ischemia in neonatal mice and the potential signaling pathway underlying these effects.ResultsCarvacrol inhibited TRPM7 current in HEK293 cells over-expressing TRPM7 and TRPM7-like current in hippocampal neurons in a dose-dependent manner. Carvacrol (>200 μM) reduced OGD-induced neuronal injury in cortical neurons. 24 hours after HI, TRPM7 protein level in the ipsilateral hemisphere was significantly higher than in the contralateral hemisphere. Carvacrol (30 and 50 mg/kg) pre-treatment reduced brain infarct volume 24 hours after HI in a dose-dependent manner. Carvacrol pre-treatment also improved neurobehavioral outcomes. Furthermore, animals pre-treated with carvacrol had fewer TUNEL-positive cells in the brain compared to vehicle-treated animals 3 days after HI. Carvacrol pre-treatment also increased Bcl-2/Bax and p-Akt/t-Akt protein ratios and decreased cleaved caspase-3 protein expression 24 hours after HI.ConclusionsCarvacrol pre-treatment protects against neonatal hypoxic-ischemic brain injury by reducing brain infarct volume, promoting pro-survival signaling and inhibiting pro-apoptotic signaling, as well as improving behavioral outcomes. The neuroprotective effect may be mediated by the inhibition of TRPM7 channel function. Carvacrol is a potential drug development target for the treatment of neonatal stroke.

BACKGROUND Immediate access to an automated external defibrillator (AED) increases the chance of survival from out-of-hospital cardiac arrest (OHCA). Current deployment usually considers spatial AED access, assuming AEDs are available 24 h a day. OBJECTIVES We sought to develop an optimization model for AED deployment, accounting for spatial and temporal accessibility, to evaluate if OHCA coverage would improve compared to deployment based on spatial accessibility alone. METHODS This was a retrospective population-based cohort study using data from the Toronto Regional RescuNET cardiac arrest database. We identified all nontraumatic public-location OHCAs in Toronto, Canada (January 2006 through August 2014) and obtained a list of registered AEDs (March 2015) from Toronto emergency medical services. We quantified coverage loss due to limited temporal access by comparing the number of OHCAs that occurred within 100 meters of a registered AED (assumed 24/7 coverage) with the number that occurred both within 100 meters of a registered AED and when the AED was available (actual coverage). We then developed a spatiotemporal optimization model that determined AED locations to maximize OHCA actual coverage and overcome the reported coverage loss. We computed the coverage gain between the spatiotemporal model and a spatial-only model using 10-fold cross-validation. RESULTS We identified 2,440 atraumatic public OHCAs and 737 registered AED locations. A total of 451 OHCAs were covered by registered AEDs under assumed 24/7 coverage, and 354 OHCAs under actual coverage, representing a coverage loss of 21.5% (p < 0.001). Using the spatiotemporal model to optimize AED deployment, a 25.3% relative increase in actual coverage was achieved over the spatial-only approach (p < 0.001). CONCLUSIONS One in 5 OHCAs occurred near an inaccessible AED at the time of the OHCA. Potential AED use was significantly improved with a spatiotemporal optimization model guiding deployment.

Historically, predicting macroscopic blood flow characteristics such as viscosity has been an empirical process due to the difficulty in rigorously including the particulate nature of blood in a mathematical representation of blood rheology. Using a two-dimensional lattice Boltzmann approach, we have simulated the flow of red blood cells in a blood vessel to estimate flow resistance at various hematocrits and vessel diameters. By including white blood cells (WBCs) in the flow, we also calculate the increase in resistance due to white cell rolling and adhesion. The model considers the blood as a suspension of particles in plasma, accounting for cell-cell and cell-wall interactions to predict macroscopic blood rheology. The model is able to reproduce the Fahraeus-Lindqvist effect, i.e., the increase in relative apparent viscosity as tube size increases, and the Fahraeus effect, i.e., tube hematocrit is lower than discharge hematocrit. In addition, the model allows direct assessment of the effect of WBCs on blood flow in the microvasculature, reproducing the dramatic increases in flow resistance as WBCs enter short capillary segments. This powerful and flexible model can be used to predict blood flow properties in any vessel geometry and with any blood composition.