111 research outputs found

    Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

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    Background Traumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats. Methods Young adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure. Results Xenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation. Conclusions Our findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma

    Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

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    Background.Xenon is a noble gas with neuroprotective properties. We previously showed that xenon improves short and long-term outcomes in young adult mice after controlled cortical impact (CCI). This is a follow-up study investigating xenon’s effect on very long-term outcome and survival. Methods.C57BL/6N (n=72) young adult male mice received single CCI or sham surgery and were treated with either xenon (75%Xe:25%O2) or control gas (75% N2:25%O2). The outcomes used were: 1) 24-hour lesion volume and neurological outcome score; 2)contextual fear-conditioning at 2 weeks and 20 months; 3) corpus callosum white matter quantification; 4) immunohistological assessment of neuroinflammation and neuronal loss; 5) long-term survival. Results.Xenon treatment significantly reduced secondary injury development (p<0.05), improved short-term vestibulomotor function (p<0.01),and prevented development of very late-onset traumatic brain injury (TBI)-related memory deficits. Xenon treatment reducedwhite matter loss in the contralateral corpus callosum and neuronal loss in the contralateral hippocampal CA1 andDG areas at 20 months. Xenon’s long-term neuroprotective effects were associated with a significant (p<0.05) reduction in neuroinflammation in multiple brain areas involved in associative memory, including reduction in reactive astrogliosis and microglial cell proliferation. Survival was improved significantly (p<0.05) in xenon-treated animals, compared to untreated animals up to 12 months after injury.Conclusions.These results show that xenon treatment after TBI results in very long-term improvements in clinically relevant outcomes and survival. Our findings support the idea that xenon treatment shortly after TBI may have long-term benefits in the treatment of brain trauma patients

    Generation Of High Non-inductive Plasma Current Fraction H-mode Discharges By High-harmonic Last Wave Heating In The National Spherical Torus Experiment

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    1.4 MW of 30 MHz high-harmonic fast wave (HHFW) heating, with current drive antenna phasing, has generated a Ip = 300kA, BT (0) = 0.55T deuterium H-mode plasma in the National Spherical Torus Experiment that has a non-inductive plasma current fraction, fNI = 0.7-1. Seventy-five percent of the non-inductive current was generated inside an internal transport barrier that formed at a normalized minor radius, r/a {approx} 0.4 . Three quarters of the non-inductive current was bootstrap current and the remaining non-inductive current was generated directly by HHFW power inside r/a {approx} 0.2
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