Yibin Chen

Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establish in vivo and in vitro models of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss in vivo. Also, in vivo, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch‐like ECH‐associated protein 1 (Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and NADPH: quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed in vitro, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides and alleviated neuronal mitochondrial injury in vitro, as indicated via tetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and mitochondrial superoxide (MitoSOX) staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in both in vivo and in vitro models of ICH, and that activation of the p62-keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

Abstract. The uptake of water by contrails in ice-supersaturated air and the release of water after ice particle advection and sedimentation dehydrates the atmosphere at flight levels and redistributes humidity mainly to lower levels. The dehydration is investigated by coupling a plume-scale contrail model with a global aerosol–climate model. The contrail model simulates all the individual contrails forming from global air traffic for meteorological conditions as defined by the climate model. The computed contrail cirrus properties compare reasonably with theoretical concepts and observations. The mass of water in aged contrails may exceed 106 times the mass of water emitted from aircraft. Many of the ice particles sediment and release water in the troposphere, on average 700 m below the mean flight levels. Simulations with and without coupling are compared. The drying at contrail levels causes thinner and longer-lived contrails with about 15 % reduced contrail radiative forcing (RF). The reduced RF from contrails is on the order of 0.06 W m−2, slightly larger than estimated earlier because of higher soot emissions. For normal traffic, the RF from dehydration is small compared to interannual variability. A case with emissions increased by 100 times is used to overcome statistical uncertainty. The contrails impact the entire hydrological cycle in the atmosphere by reducing the total water column and the cover by high- and low-level clouds. For normal traffic, the dehydration changes contrail RF by positive shortwave and negative longwave contributions on the order of 0.04 W m−2, with a small negative net RF. The total net RF from contrails and dehydration remains within the range of previous estimates.