We previously demonstrated maladaptive remodeling characteristic

We previously demonstrated maladaptive remodeling characteristic of IA initiation occurring

in hemodynamic regions of combined high wall shear stress (WSS) and high WSS gradient near the apex of an experimentally created carotid bifurcation. This study examines whether this remodeling recapitulates the molecular changes found in IAs and whether molecular changes also correspond to specific hemodynamic environments.

METHODS: De novo bifurcations were surgically created using Selleckchem DihydrotestosteroneDHT both native common carotid arteries in each of 6 dogs. Bifurcations were imaged 2 weeks or 2 months after surgery by high-resolution 3-dimensional angiography, from which flow fields were obtained by computational fluid dynamics simulations. Subsequently,

harvested tissues, demonstrating early aneurysmal changes near the apex, were immunostained for interleukin-1 beta, endothelial and inducible nitric oxide synthases, nitrotyrosine, and matrix metalloproteinase-2 and -9. Spatial distributions E7080 order of these molecules were comapped with computational fluid dynamics results.

RESULTS: The aneurysmal wall showed decreased endothelial nitric oxide synthase expression compared with surrounding segments, the feeding artery, and native controls, whereas all other markers increased. Anti-CD68 staining indicated the absence of inflammatory cells in the aneurysmal wall. Comapping molecular marker distributions with flow fields revealed confinement of these molecular changes within the hemodynamic region of high WSS and high, positive WSS gradient.

CONCLUSION: Aneurysm-initiating

remodeling induced by combined high WSS and high, positive WSS gradient is associated with molecular changes implicated in IAs.”
“OBJECTIVE: Our previous studies demonstrated that simvastatin promotes neurological functional recovery after traumatic brain injury (TBI) in rat; however, the underlying mechanisms remain poorly understood. The purpose of this study was to investigate the anti-inflammatory effect of simvastatin by measuring the level of cytokines and activation ROS1 of glial cells.

METHODS: Controlled cortical impact injury was performed in adult male Wistar rats. The rats were randomly divided into 3 groups: sham, saline control group, and simvastatin treatment group. Simvastatin was administered orally starting at day 1 after TBI until animals were killed at days 1, 3, 7, 14, and 35 after treatment. Functional outcome was measured using modified neurological severity scores. Enzyme-linked immunosorbent assay and immunohistochemical staining were used to measure the expression of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-a and to identify activated microglial cells and astrocytes.

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