No abstract

The NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays a critical role in protecting against oxidative stress in brain ischemia and reperfusion injury. Glycogen synthase kinase 3β (GSK-3β) may play a critical role in regulating Nrf2 in a Kelch-like ECH-associated protein 1 (Keap1)-independent manner. However, the relationship between GSK-3β and Nrf2 in brain ischemia and reperfusion injury is not clear. In this study, we explored the mechanisms through which GSK-3β regulates Nrf2 and Nrf-2/ARE pathways in vitro and in vivo. We used oxygen and glucose deprivation/reoxygenation (OGD/R) in primary cultured cortical neurons and a middle cerebral artery occlusion-reperfusion (MCAO/R) rat model to mimic ischemic insult. In this study, GSK-3β siRNA and inhibitors (SB216763 and LiCl) were used to inhibit GSK-3β in vitro and in vivo. After inhibiting GSK-3β, expression of total and nuclear Nrf2, Nrf2-ARE binding activity, and expression of Nrf2/ARE pathway-driven genes HO-1 and NQO-1 increased. Overexpression of GSK-3β yielded opposite results. These results suggest that GSK-3β downregulates Nrf2 and the Nrf2/ARE pathway in brain ischemia and reperfusion injury. GSK-3β may be an endogenous antioxidant relevant protein, and may represent a new therapeutic target in treatment of ischemia and reperfusion injury.

No abstract

No abstract

No abstract

No abstract

No abstract

The current study aims to investigate the effectiveness of two different designs of helmet interior cushion, (Helmet 1: strap-netting; Helmet 2: Oregon Aero foam-padding), and the effect of the impact directions on the helmeted head during ballistic impact. Series of ballistic impact simulations (frontal, lateral, rear, and top) of a full-metal-jacketed bullet were performed on a validated finite element head model equipped with the two helmets, to assess the severity of head injuries sustained in ballistic impacts using both head kinematics and biomechanical metrics. Benchmarking with experimental ventricular and intracranial pressures showed that there is good agreement between the simulations and experiments. In terms of extracranial injuries, top impact had the highest skull stress, still without fracturing the skull. In regard to intracranial injuries, both the lateral and rear impacts generally gave the highest principal strains as well as highest shear strains, which exceed the injury thresholds. Off-cushion impacts were found to be at higher risk of intracranial injuries. The study also showed that the Oregon Aero foam pads helped to reduce impact forces. It also suggested that more padding inserts of smaller size may offer better protection. This provides some insights on future's helmet design against ballistic threats.