Abstract Electrostatic fluctuations driven by runaway electrons (REs) have been observed following a thermal quench during Experimental Advanced Superconducting Tokamak–intended disruptions, which are triggered by massive gas injection. Electrostatic fluctuations are clearly detected using several radiation-related diagnostics and in two distinct frequency bands: 10–20 kHz and 30–40 kHz. The appearances of fluctuations are directly correlated with REs. Fluctuations observed during argon injection and neon injection have significantly different evolution with time, whereas no fluctuations can be found with helium injection. The measured frequency scales with different amounts of injected gases finally tend to be saturated. A clear phase difference is detected, and a mode structure of ( m, n ) = (1, 0) is identified in the soft x-ray detector array. Here, m and n are the poloidal and toroidal mode numbers, respectively. The geodesic acoustic mode proposed as a candidate instability is further discussed, and the barely trapped/passing electrons can contribute to drive the mode. Fluctuations are also correlated with significant RE loss, which supports the possibility of kinetic instability for RE mitigation in a tokamak reactor.
Oxidative stress plays an important role in the pathological processes of ischemic brain damage. Many antioxidants have been shown to protect against cerebral ischemia injury by inhibiting oxidative stress both in vitro and in vivo. 20-Hydroxyecdysone (20E), an ecdysteroid hormone, exhibits antioxidative effects. For the work described in this paper, we used an in vitro oxidative damage model and an in vivo ischemic model of middle cerebral artery occlusion (MCAO) to investigate the neuroprotective effects of 20E and the mechanisms related to these effects. Treatment of cells with H2O2 led to neuronal injury, intracellular ROS/RNS generation, mitochondrial membrane potential dissipation, cellular antioxidant potential descent, an increase in malondialdehyde (MDA) and an elevation of intracellular [Ca2+], all of which were markedly attenuated by 20E. Inhibition of the activation of the ASK1-MKK4/7-JNK stress signaling pathway and cleaved caspase-3 induced by oxidative stress were involved in the neuroprotection afforded by 20E. In addition, 20E reduced the expression of iNOS protein by inhibition of NF-κB activation. The neuroprotective effect of 20E was also confirmed in vivo. 20E significantly decreased infarct volume and the neurological deficit score, restored antioxidant potential and inhibited the increase in MDA and TUNEL-positive and cleaved caspase-3-positive cells in the cerebral cortex in MCAO rats. Together, these results support that 20E protects against cerebral ischemia injury by inhibiting ROS/RNS production and modulating oxidative stress-induced signal transduction pathways.
OBJECTIVE: To construct the Fas ligand (FasL) and inducible nitric oxide synthase (iNOS) coexpressed PCA 13 plasmid used for packing of adenovirus, so as to observe the immunoprotective effect of FasL on the adenovirus vector. METHODS: By way of the internal ribosome entry site (IRES), gene engineering techniques such as preparation and transformation of competent cells, plasmid extraction, agarose gel electrophoresis and restriction enzymolysis were used for the construction of the polycistron adenoviral expression vector PCA 13 /FasL–IRES–iNOS, which could coexpress FasL and the iNOS gene after multisubcloning steps. RESULTS: FasL and iNOS connected with the IRES were successfully cloned to the PCA 13 plasmid and verified by enzymolysis (600 bp FasL, 1000 bp IRES and 4000 bp iNOS) and the gene sequence was concordant with the gene bank. CONCLUSIONS: The polycistron adenoviral expression vector PCA 13 /FasL–IRES–iNOS was successfully constructed.
Abstract Nitric oxide (NO), a free radical with signaling functions in the CNS, is implicated in some developmental processes, including neuronal survival, precursor proliferation, and differentiation. However, neuronal nitric oxide synthase (nNOS) ‐derived NO and inducible nitric oxide synthase (iNOS) ‐derived NO play opposite role in regulating neurogenesis in the dentate gyrus after cerebral ischemia. In this study, we show that focal cerebral ischemia reduced nNOS expression and enzymatic activity in the hippocampus. Ischemia‐induced cell proliferation in the dentate gyrus was augmented in the null mutant mice lacking nNOS gene (nNOS−/−) and in the rats receiving 7‐nitroindazole, a selective nNOS inhibitor, after stroke. Inhibition of nNOS ameliorated ischemic injury, up‐regulated iNOS expression, and enzymatic activity in the ischemic hippocampus. Inhibition of nNOS increased and iNOS inhibitor decreased cAMP response element‐binding protein phosphorylation in the ipsilateral hippocampus in the late stage of stroke. Moreover, the effects of 7‐nitroindazole on neurogenesis after ischemia disappeared in the null mutant mice lacking iNOS gene (iNOS−/−). These results suggest that reduced nNOS is involved in ischemia‐induced hippocampal neurogenesis by up‐regulating iNOS expression and cAMP response element‐binding protein phosphorylation.
Abstract Neurogenesis in the adult mammalian hippocampus may contribute to repairing the brain after injury. The signals that regulate neurogenesis in the dentate gyrus following ischemic stroke insult are not well known. We have previously reported that inducible nitric oxide synthase (iNOS) expression is necessary for ischemia‐stimulated neurogenesis in the adult dentate gyrus. Here, we show that mice subjected to 90 min of middle cerebral artery occlusion (MCAO) significantly increased the number of new neurons and up‐regulated iNOS expression in the dentate gyrus. Blockade of the L‐type voltage‐gated Ca 2+ channel (L‐VGCC) prevented neurogenesis in the dentate gyrus and subventricular zone (SVZ), and down‐regulated iNOS expression in the dentate gyrus after cerebral ischemia. This study suggests that Ca 2+ influx through L‐VGCC is involved in ischemia‐induced neurogenesis by up‐regulating iNOS expression.
20-Hydroxyecdysone, which is found in the rhizomes, roots and the stems of many plants, is an ecdysteroid hormone that regulates molting in insects. We have previously shown that 20-Hydroxyecdysone could alleviate neurological deficits induced by subarachnoid hemorrhage in rabbits. Thus, we hypothesized that 20-Hydroxyecdysone might protect neurons against hypoxic-ischemic injury. In present study, the effects of 20-Hydroxyecdysone on cobalt chloride (CoCl(2))-induced cellular injury in PC12 cells was investigated. The incubation of PC12 cells with CoCl(2) reduced the cell viability, increased the rate of apoptosis. However, when cells were treated with 20-Hydroxyecdysone before or after CoCl(2) exposure, the CoCl(2)-induced cellular injuries were significantly ameliorated. In addition, 20-Hydroxyecdysone dramatically reduced the CoCl(2)-induced production of reactive oxygen species (ROS), decreased the depolarization of the mitochondrial membrane, inhibited the release of cytochrome c into the cytosol and increased the Bax/Bcl-2 ratio. Furthermore, 20-Hydroxyecdysone eliminated the CoCl(2)-induced activation of caspase-3. Taken together, these results indicate that 20-Hydroxyecdysone may protect PC12 cells against CoCl(2)-induced cell injury by inhibiting ROS production and modulating components of the mitochondrial apoptosis pathway. Based on our results, 20-Hydroxyecdysone may be a potential candidate for intervention in hypoxic-ischemic brain injuries such as stroke.
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