Proposition d’un modèle animal de psychose schizophréniforme sur la base des troubles de la neurotransmission et du comportement spontané du rat soumis aux hautes pressions

La schizophrénie est une maladie psychiatrique d’évolution chronique ayant pourconséquences des altérations de la perception de la réalité, des troubles cognitifs et des dysfonctionnements sociaux et comportementaux plus ou moins importants. Des travaux antérieurs de neurochimie et neuropharmacologie du comportement spontané chez l’animal soumis aux hautes pressions ont montré l’existence d’une corrélation significative entre les perturbations du système nerveux par les hautes pressions et celles exprimées chez les malades schizophrènes. Une telle analogie pourrait constituer un outil de base pour la proposition d’un modèle animal de cette pathologie. Ce modèle est basé sur des données concernant des altérations de la neurotransmission dopaminergique (augmentation de la libération de dopamine, altération fonctionnelle de type blocage des récepteurs D1 et D2 présynaptiques et potentialisation de l’activité des récepteurs D2 postsynaptiques) et acido-aminergique (diminution de la libération du glutamate, et potentialisation de l’activité des récepteurs NMDA). Ce modèle constitue un outil utile pour l’étude des mécanismes biologiques de la schizophrénie et du développement de nouvelles molécules antipsychotiques

Tirofiban, a Glycoprotein IIb/IIIa Antagonist, Has a Protective Effect on Decompression Sickness in Rats: Is the Crosstalk Between Platelet and Leukocytes Essential?

In its severest forms, decompression sickness (DCS) may extend systemically and/or induce severe neurological deficits, including paralysis or even death. It seems that the sterile and ischemic inflammatory phenomena are consecutive to the reaction of the bubbles with the organism and that the blood platelet activation plays a determinant role in the development of DCS. According to the hypotheses commonly put forward, the bubbles could either activate the platelets by direct contact or be the cause of abrasion of the vascular epithelium, which would expose the basal plate glycogen and then prompt the platelets to activate. The purpose of this study is to confirm anti-platelet drugs specific to GPIIb/IIIa integrin could prevent DCS, using a rat model. There is a significant difference concerning the incidence of the drug on the clinical status of the rats (p = 0.016), with a better clinical outcome for rats treated with tirofiban (TIR) compared with the control rats (p = 0.027), even if the three anti-GPIIb/IIIa agents used have limited respiratory distress. TIR limited the decrease in platelet counts following the hyperbaric exposure. TIR help to prevent from DCS. TIR is specific to GPIIb/IIIa whereas eptifibatide and abciximab could inhibit αVβ3 and αMβ2 involved in communication with the immune system. While inhibiting GPIIb/IIIa could highlight a platelet-dependent inflammatory pathway that improves DCS outcomes, we wonder whether inhibiting the αVβ3 and αMβ2 communications is not a wrong approach for limiting mortality in DCS

Nitrogen at raised pressure interacts with the GABAA receptor to produce its narcotic pharmacological effect in the rat

Background: Strong evidence supports the concept that conventional anesthetics, including inhalational agents and inert gases, such as xenon and nitrous oxide, interact directly with ion channel neurotransmitter receptors. However, there is no evidence that nitrogen, which only exhibits narcotic potency at increased pressure, may act by a similar mechanism. Methods: We compared the inhibitory and sedative effects of ␥-aminobutyric acid (GABA) and nitrogen pressure on locomotor activity and striatal dopamine release in freely moving rats and investigated the pharmacologic properties of the GABAinduced and nitrogen pressure-induced narcotic action using the highly selective competitive GABA A receptor antagonist bicuculline. Results: Intracerebroventricular GABA infusion up to 60 mol or exposure to nitrogen pressure up to 3 MPa decreased to a similar extent striatal dopamine release (

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<p>Hyperbaric oxygen increases tissue-plasminogen activator-induced thrombolysis in vitro, and reduces ischemic brain damage and edema in rats subjected to thromboembolic brain ischemia</p

Human recombinant tissue-plasminogen activator (alteplase): why not use the ‘human' dose for stroke studies in rats?

Since a pioneer work that has shown in vitro that the rat's fibrinolytic system is 10-fold less sensitive to recombinant tissue-plasminogen activator (rtPA) than the human system, most preclinical studies are performed with 10 instead of 0.9 mg/kg rtPA (the clinical dose in stroke patients). In this study, we compared the effects of these doses on mean time to reperfusion, reperfusion slope, brain infarct volume and edema in a rat model of thrombo-embolic stroke. Our data provide evidence that the dose of 0.9 mg/kg rtPA is as appropriate as that of 10 mg/kg for preclinical stroke studies in rodents

Comment la bio-cristallographie permet de proposer un mécanisme d’action des gaz anesthésiques

Les gaz inertes sont utilisés pour leurs propriétés anesthésiques. Récemment, la découverte de leurs propriétés neuroprotectrices a relancé les recherches sur les mécanismes moléculaires mis en jeu, encore mal connus. Nous avons déterminé, sous pression de xénon ou de protoxyde d’azote, la structure de l’urate oxydase et de l’annexine V, deux protéines modèles de celles impliquées dans l’anesthésie. Cette étude a montré que ces deux gaz occupaient le même site de liaison principal. Les relations observées entre l’expansion du volume des cavités de liaison des gaz et leurs pouvoirs anesthésiants ont permis de proposer un mécanisme d’action en deux étapes

Pressure-Induced Disorders in Neurotransmission and Spontaneous Behavior in Rats: An Animal Model of Psychosis

Disorders in neurotransmission and spontaneous behavior in rats exposed to a high pressure helium-oxygen mixture that shows interesting parallels with the dopaminergic hypothesis of schizophrenia at both the biochemical and the therapeutic responding levels are reviewed. Furthermore, as human subjects exposed to a very high pressure have shown psychotic episodes, we conclude that the pressure-induced disorders in neurotransmission and spontaneous behavior in rats could constitute a valid animal model of schizophreniform psychosis and a useful tool for both the investigation of the biological mechanisms underlying schizophrenia and the development of new antipsychotic drugs