The effects of strong shock waves on mortality rates and percentages of pulmonary lesions in rats as a function of the number of exposures

The results of the study reveal that with regard to the pulmonary lesions, twice the number of exposures is compensated for by quartering the overpressure of the wave crest. With regard to the mortality rates, it reveals that halving the overpressure of the wave crest is offset by a 20-fold increase in the number of exposures

Ketamine enhances structural plasticity in mouse mesencephalic and human iPSC-derived dopaminergic neurons via AMPAR-driven BDNF and mTOR signaling

Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons. Sixty minutes exposure to ketamine elicited concentration-dependent increases of dendritic arborization and soma size in both mouse and human cultures as measured 72 hours after application. These structural effects were blocked by mTOR complex/signaling inhibitors like rapamycin. Direct evidence of mTOR activation by ketamine was revealed by its induction of p70S6 kinase. All effects of ketamine were abolished by AMPA receptor antagonists and mimicked by the AMPA-positive allosteric modulator CX614. Inhibition of BDNF signaling prevented induction of structural plasticity by ketamine or CX614. Furthermore, the actions of ketamine required functionally intact dopamine D3 receptors (D3R), as its effects were abolished by selective D3R antagonists and absent in D3R knockout preparations. Finally, the ketamine metabolite (2R,6R)-hydroxynorketamine mimicked ketamine effects at sub-micromolar concentrations. These data indicate that ketamine elicits structural plasticity by recruitment of AMPAR, mTOR and BDNF signaling in both mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons. These observations are of likely relevance to the influence of ketamine upon mood and its other functional actions in vivo.Molecular Psychiatry advance online publication, 21 November 2017; doi:10.1038/mp.2017.241

ÉTUDE DU RÉFLEXE DE PROTECTION COCHLÉAIRE IPSILATÉRAL

L'amplitude des élévations des seuils auditifs engendrés par des bruits impulsionnels est fonction du rythme de présentation de ces bruits. Cet effet peut être le reflet d'une protection cochléaire agissant par l'intermédiaire du système efférent. Nous avons exposé des cobayes tricolores à des bruits impulsionnels (bouffées de bruit de 8 kHz, temps de monté et de descente 0,4 ms, durée du pateau 10 ms) soit à un rythme de présentation de 17/s pendant 1 mn, soit à un rythme de 1/s pendant 17 mn, à des niveaux de stimulation compris entre 131 et 147 dB SPL. Les stimulations acoustiques sont délivrées en circuit fermé sur l'oreille gauche des animaux. Le rythme de présentation de 1/s provoque la plus grande élévation de seuils ipsilatérale. L'effet du réflexe de Protection acoustique de l'oreille moyenne ne peut être mis en cause étant donné que les variations des seuils auditifs observées ne sont pas modifiées par la curarisation des animaux. L'injection intrapéritonéale de scopolamine ou de strychnine, chez des animaux exposés à un rythme de 17/s induit une augmentation notable des seuils auditifs. Ces résultats indiquent qu'un mécanisme de protection cochléaire mettant en cause le système efférent cholinergique est envisageable. L'utilisation de diverses stimulations acoustiques (présentation temporelle, fréquence etc ...) ainsi que la section des voies efférentes au niveau du plancher du IVème ventricule devraient nous permettre de confirmer cette hypothèse.The Threshold Shifts (TS) induced by impulse noises depend on the rythm of presentation. Because this effect is prevent even when the action of the middle ear muscles is impaired, it could be due to an intracochlear acoustic reflex elicited by the efferent feedback (Buck, Dancer et Franke, J. Acoust., 1984). We have exposed coloured guinea pigs (mean weight : 350 g) to the same number of 8 kHz tone bursts (total duration : 10,8 ms, rise and fall times : 0,4 ms) either at a rythm of seventeen per second during one minute or at a rythm of one per second during seventeen minutes. In the second exposure condition (one second interval) the largest part of the protective effects elicited by a given tone-burst would have vanished before the following tone-burst occurs. The level of the acoustic stimulation ranged from 131 to 147 db SPL. All animals were anesthetized with Ketamine and their body temperature was kept constant during all the experiment with the help of a heating blanket. The stimuli were delivered in closed circuit on the left ear only. Electrocochleographic recordings (4 to 32 kHz) performed on this same ear allowed to measure the TS twenty minutes after the end of each exposure (by comparison with the pre-exposure thresholds in the same animals). For a given exposure level, the largest ipsilateral TS are measured when the presentation rythm is of one per second. The effect of the acoustic reflex of the middle ear on these TS cm be ruled out because TS remain unchanged when the animals were curarized prior the exposure to the same acoustic stimulation. The intraperitoneal injection of scopolamine or strychnine induces larger TS. These results indicate that a protective intracochlear mechanism is mediated via the efferent cholinergic system. The same kind of measurements will also be performed after section of the efferent pathways on the floor of the 4th ventricule

APPROACH OF THE INTRACOCHLEAR ACOUSTIC REFLEX IN THE GUINEA PIG

No abstract availabl