Brain insults are a major cause of acute mortality and chronic morbidity. Given the largely ineffective current therapeutic strategies, the development of new and efficient therapeutic interventions is clearly needed. A series of previous investigations has shown that the noble and anesthetic gas xenon, which has low-affinity antagonistic properties at the N-methyl-D-aspartate (NMDA) receptor, also exhibits potentially neuroprotective properties with no proven adverse side effects. Surprisingly and in contrast with most drugs that are being developed as therapeutic agents, the dose-response neuroprotective effect of xenon has been poorly studied, although this effect could be of major critical importance for its clinical development as a neuroprotectant. Here we show, using ex vivo and in vivo models of excitotoxic insults and transient brain ischemia, that xenon, administered at subanesthetic doses, offers global neuroprotection from reduction of neurotransmitter release induced by ischemia, a critical event known to be involved in excitotoxicity, to reduction of subsequent cell injury and neuronal death. Maximal neuroprotection was obtained with xenon at 50 vol%, a concentration at which xenon further exhibited significant neuroprotective effects in vivo even when administered up to 4 h after intrastriatal NMDA injection and up to at least 2 h after induction of transient brain ischemia.

This paper describes a technique that combines radial MRI and phase contrast (PC) to map the velocities of hyperpolarized gases ( 3 He) in respiratory airways. The method was evaluated on well known geometries (straight and U-shaped pipes) before it was applied in vivo. Dynamic 2D maps of the three velocity components were obtained from a 10-mm slice with an in-plane spatial resolution of 1.6 mm within 1 s. Integration of the in vitro throughplane velocity over the slice matched the input flow within a relative precision of 6.4%. As expected for the given Reynolds number, a parabolic velocity profile was obtained in the straight pipe. In the U-shaped pipe the three velocity components were measured and compared to a fluid-dynamics simulation so the precision was evaluated as fine as 0.025 m s ؊1. Ventilation and particle-deposition studies are important parts of functional and physiological explorations of the lungs. Normal or altered geometries of the bronchial tree directly affect airflow distributions in the lungs (1). Particle deposition is involved in inhalation toxicology, and its study is motivated to achieve a better understanding of its effects and devise new therapies based on drug inhalation (2,3). Knowledge of flow patterns in large tracheobronchial airways is required to understand flow distribution, gas mixing, and inhaled particle deposition.Several experimental and numerical studies have focused on the velocity patterns in large airways. Experimentally, velocity fields in various airway models were obtained with the available techniques for measuring gas velocity, including hot-wire anemometry, laser Doppler anemometry, and particle-image velocimetry (4 -6). Numerical simulations were also performed with computational fluid dynamics (CFD) (2,6 -8). Both approaches independently yielded basic results that led to a better understanding of gas-flow dynamics in the bronchi. However, in vivo, functional respiratory tests provide only global information on the airflow, and some invasive techniques introduce sensors to probe flow properties locally but only at a few specific points (9). Nevertheless, noninvasive direct measurements of gas velocities have never been obtained in living subjects, since none of the abovecited measurement techniques are able to do so.Recently it was shown that ventilation dynamics in the lungs of small animals and humans can be monitored by hyperpolarized (HP) gas MRI (10) using EPI (11), fast gradient-echo (12), spiral (13,14), or radial sequences (15,16). However, quantifying the gas-flow rate from signal dynamics is not straightforward because it is difficult to separate flip angle and inflow effects (12,(17)(18)(19). Moreover, additional signal losses result from oxygen-dependent longitudinal relaxation times that become relevant over long acquisition times (20), and from short effective transverse relaxation times, while the gas diffuses through the magnetic field gradients within the airways (21,22).In proton MRI, phase contrast (PC) has been widely used to map blood v...

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Nitrous oxide (N(2)O), a pharmacological active gas and an antagonist of N-methyl-D-aspartic acid receptors, has been reported to be effective in the treatment of alcohol and tobacco withdrawal syndrome. However, the neurobiological bases of N(2)O effects are unknown. The aim of the present studies was to examine the effect of N(2)O on acquisition and expression of morphine- (10 mg/kg; s.c.) and cocaine- (20 mg/kg; i.p.) induced conditioned place preference (CPP) in mice. Unbiased place conditioning method was used. Mice were exposed to N(2)O during the conditioning phase (acquisition of CPP) or during postconditioning phase (expression of CPP). The same protocol was used to evaluate the impact of N(2)O on locomotor activity, two-trial recognition task (memory), spontaneous alternation, sucrose consumption (anhedonic state), forced swim (depressive state) and elevated O-maze tests (anxiety state). In all these tests, mice were treated with morphine (10 mg/kg, s.c.) the first day, the following day mice were given saline. This sequence alternated during the next 4 days. Control animals received saline every day. The behavior of animals was evaluated on day 8. N(2)O did not induce CPP but impaired the acquisition of morphine-induced CPP and blocked the expression of cocaine- and morphine-induced CPP. The effects of the gas were long lasting and persist 4 days following the exposure. Moreover no behavioral modifications in tests usually used to investigated emotional state as compared with control mice were observed in animals exposed to N(2)O, ruling out an effect of this gas on attention, anxiety, depression, locomotion and anhedonia. These studies raise the possibility that N(2)O could have a clinical benefit in the management of morphine and cocaine addiction.

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