27 results on '"Chuquet J"'
Search Results
2. COMPARTMENTALIZATION OF GLUCOSE UPTAKE BETWEEN ASTROCYTES AND NEURONS IN VIVO: S15-03
- Author
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Chuquet, J.
- Published
- 2013
3. Prolonged deficit of gamma oscillations in the peri-infarct cortex of mice after stroke
- Author
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Hazime, M, primary, Alasoadura, M, additional, Lamtahri, R, additional, Quilichini, P, additional, Leprince, J, additional, Vaudry, D, additional, and Chuquet, J, additional
- Published
- 2020
- Full Text
- View/download PDF
4. Orexigenic neuropeptide 26RFa: new evidence for an adaptive profile of appetite regulation in anorexia nervosa
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Fauquembergue, Emilie, Toutirais, Olivier, Tougeron, David, Drouet, Aurélie, Le Gallo, Matthieu, Desille, Mireille, Cabillic, Florian, De La Pintière, Cécile Thomas, Iero, Manuela, Rivoltini, Licia, Baert-Desurmont, Stéphanie, Vaudry, Hubert, Sesboüe, Richard, Frebourg, Thierry, Latouche, Jean-Baptiste, Catros, Véronique, Gach, D, Belkacemi, D, Lefranc, R, Perlikowski, D, Masson, J., Walet-Balieu, R, Do-Rego, J., Galas, R, Schapman, D., Lamtahri, D, Tonon, D, Vaudry, D., Chuquet, J., Gach, K., Belkacemi, O., Lefranc, B., Perlikowski, P., Walet-Balieu, M.-L., Galas, L., Lamtahri, R., Tonon, M.-C., Galusca, Bogdan, Jeandel, Lydie, Germain, Natacha, Alexandre, David, Leprince, Jérôme, Anouar, Youssef, Estour, Bruno, Chartrel, Nicolas, Biothérapies Innovantes, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), CRLCC Eugène Marquis (CRLCC), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori-IRCCS Foundation, Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Endocrinologie, Centre Hospitalier Universitaire de Saint-Etienne, Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
- Subjects
food intake ,Anorexia Nervosa ,Endocrinology, Diabetes and Metabolism ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Clinical Biochemistry ,Appetite ,diazepam-binding inhibitor ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,MESH: Neuropeptides ,Biochemistry ,0302 clinical medicine ,Endocrinology ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Medicine ,Bulimia ,media_common ,2. Zero hunger ,0303 health sciences ,digestive, oral, and skin physiology ,MESH: Energy Metabolism ,anxiety ,Adaptation, Physiological ,Ghrelin ,Circadian Rhythm ,Eating disorders ,Anorexia nervosa (differential diagnoses) ,MESH: Young Adult ,Female ,medicine.symptom ,MESH: Anorexia Nervosa ,hormones, hormone substitutes, and hormone antagonists ,MESH: Malnutrition ,Binge-Eating Disorder ,medicine.drug ,Adult ,medicine.medical_specialty ,phosphorylated peptide ,MESH: Rats ,Adolescent ,media_common.quotation_subject ,MESH: Ghrelin ,030209 endocrinology & metabolism ,Context (language use) ,03 medical and health sciences ,endozepines ,Young Adult ,MESH: Cross-Sectional Studies ,Internal medicine ,Orexigenic ,Humans ,Circadian rhythm ,MESH: Bulimia ,MESH: Circadian Rhythm ,030304 developmental biology ,MESH: Adolescent ,MESH: Humans ,Binge eating ,business.industry ,Biochemistry (medical) ,Malnutrition ,Neuropeptides ,MESH: Adult ,MESH: Binge-Eating Disorder ,medicine.disease ,MESH: Adaptation, Physiological ,Cross-Sectional Studies ,octadecaneuropeptide ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,MESH: Appetite ,business ,Energy Metabolism ,MESH: Female - Abstract
Restrictive anorexia nervosa (AN) presents an adaptive appetite regulating profile including mainly high levels of ghrelin. Because this adaptive mechanism is not effective on food intake, other appetite-regulating peptides need to be explored. 26RFa is a hypothalamic neuropeptide that stimulates appetite, gonadotropin release, and bone metabolism.The objective of the study was to evaluate the circadian levels of 26RFa in AN patients compared with healthy subjects, other eating disorders, and constitutional thinness (CT).This was a cross-sectional study performed in an endocrine unit and an academic laboratory.Five groups of age-matched young women were included in the study: 19 restrictive AN, 10 AN with bingeing/purging episodes, 14 with CT, 10 bulimic, and 10 normal-weight controls.Twelve-point circadian profiles of plasma 26RFa levels were measured in each subject.Significant circadian variations of 26 RFA were noticed in controls with higher values in the morning and abrupt decrease at noon. Twenty-four-hour mean 26RFa levels were significantly increased in restrictive AN and AN with bingeing/purging episodes (P0.001), predominantly in the afternoon and evening when compared with controls. Preprandial rises of 26 RFA were noticed in AN patients. Mean 26RFa levels trend to be higher in CT than in controls (P = 0.06) and significantly lower than in AN. The bulimic patients presented a circadian profile of 26RFa similar to that of controls.High levels of circulating 26RFa observed in AN patients might reflect an adaptive mechanism of the organism to promote energy intake and to increase fat stores in response to undernutrition.
- Published
- 2012
5. Detection, characterization and biological activities of [bisphospho-thr3,9]ODN, an endogenous molecular form of ODN released by astrocytes
- Author
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Gach, K., primary, Belkacemi, O., additional, Lefranc, B., additional, Perlikowski, P., additional, Masson, J., additional, Walet-Balieu, M.-L., additional, Do-Rego, J.-C., additional, Galas, L., additional, Schapman, D., additional, Lamtahri, R., additional, Tonon, M.-C., additional, Vaudry, D., additional, Chuquet, J., additional, and Leprince, J., additional
- Published
- 2015
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6. L’Absence mérite-t-elle un zéro
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DESCHAMPS, ALAIN, Chuquet, J., DESCHAMPS, ALAIN, In G. Deléchelle, M. Fryd, Centre de Linguistique Inter-langues, de Lexicologie, de Linguistique Anglaise et de Corpus (CLILLAC-ARP (EA_3967)), and Université Paris Diderot - Paris 7 (UPD7)
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pédagogie ,[SHS.LANGUE]Humanities and Social Sciences/Linguistics ,[SHS.LANGUE] Humanities and Social Sciences/Linguistics ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 1997
7. Temps et Aspect en Indonésien
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Steinhauer, H., Chuquet, J., Grangé, Ph., Steinhauer, H., Chuquet, J., and Grangé, Ph.
- Abstract
Université de Poitiers, 25 november 2006, Promotores : Steinhauer, H., Chuquet, J., Item does not contain fulltext
- Published
- 2006
8. Tissue-type plasminogen activator crosses the intact blood-brain barrier by low-density lipoprotein receptor-related protein-mediated transcytosis.
- Author
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Benchenane K, Berezowski V, Ali C, Fernández-Monreal M, López-Atalaya JP, Brillault J, Chuquet J, Nouvelot A, MacKenzie ET, Bu G, Cecchelli R, Touzani O, and Vivien D
- Published
- 2005
9. Potential mechanisms of interleukin-1 involvement in cerebral ischaemia
- Author
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Touzani, O., Boutin, H., Chuquet, J., and Rothwell, N.
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- 1999
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10. Les rickettsioses des Bovidés et équidés dans le département du Calvados
- Author
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Pitre, Jean, primary and Chuquet, J., additional
- Published
- 1960
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11. Vascular Response to Spreading Depolarization Predicts Stroke Outcome.
- Author
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Binder NF, Glück C, Middleham W, Alasoadura M, Pranculeviciute N, Wyss MT, Chuquet J, Weber B, Wegener S, and El Amki M
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- Animals, Cerebrovascular Circulation, Humans, Infarction, Mice, Cortical Spreading Depression physiology, Hyperemia, Stroke diagnostic imaging, Stroke drug therapy
- Abstract
Background: Cortical spreading depolarization (CSD) is a massive neuro-glial depolarization wave, which propagates across the cerebral cortex. In stroke, CSD is a necessary and ubiquitous mechanism for the development of neuronal lesions that initiates in the ischemic core and propagates through the penumbra extending the tissue injury. Although CSD propagation induces dramatic changes in cerebral blood flow, the vascular responses in different ischemic regions and their consequences on reperfusion and recovery remain to be defined., Methods: Ischemia was performed using the thrombin model of stroke and reperfusion was induced by r-tPA (recombinant tissue-type plasminogen activator) administration in mice. We used in vivo electrophysiology and laser speckle contrast imaging simultaneously to assess both electrophysiological and hemodynamic characteristics of CSD after ischemia onset. Neurological deficits were assessed on day 1, 3, and 7. Furthermore, infarct sizes were quantified using 2,3,5-triphenyltetrazolium chloride on day 7., Results: After ischemia, CSDs were evidenced by the characteristic propagating DC shift extending far beyond the ischemic area. On the vascular level, we observed 2 types of responses: some mice showed spreading hyperemia confined to the penumbra area (penumbral spreading hyperemia) while other showed spreading hyperemia propagating in the full hemisphere (full hemisphere spreading hyperemia). Penumbral spreading hyperemia was associated with severe stroke-induced damage, while full hemisphere spreading hyperemia indicated beneficial infarct outcome and potential viability of the infarct core. In all animals, thrombolysis with r-tPA modified the shape of the vascular response to CSD and reduced lesion volume., Conclusions: Our results show that different types of spreading hyperemia occur spontaneously after the onset of ischemia. Depending on their shape and distribution, they predict severity of injury and outcome. Furthermore, our data show that modulating the hemodynamic response to CSD may be a promising therapeutic strategy to attenuate stroke outcome.
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- 2022
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12. The Gliopeptide ODN, a Ligand for the Benzodiazepine Site of GABA A Receptors, Boosts Functional Recovery after Stroke.
- Author
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Lamtahri R, Hazime M, Gowing EK, Nagaraja RY, Maucotel J, Alasoadura M, Quilichini PP, Lehongre K, Lefranc B, Gach-Janczak K, Marcher AB, Mandrup S, Vaudry D, Clarkson AN, Leprince J, and Chuquet J
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- Adult, Animals, Astrocytes metabolism, Cortical Spreading Depression physiology, Diazepam Binding Inhibitor deficiency, Diazepam Binding Inhibitor physiology, Drug Implants, Evoked Potentials, Somatosensory, Female, GABA-A Receptor Agonists pharmacology, Humans, Hydrogels, Infarction, Middle Cerebral Artery drug therapy, Intracranial Thrombosis drug therapy, Intracranial Thrombosis etiology, Light, Mice, Mice, Inbred C57BL, N-Methylaspartate toxicity, Neurons physiology, Neuropeptides deficiency, Neuropeptides physiology, Patch-Clamp Techniques, Peptide Fragments deficiency, Peptide Fragments physiology, Rats, Rose Bengal radiation effects, Rose Bengal toxicity, Single-Blind Method, Stroke etiology, Diazepam Binding Inhibitor therapeutic use, GABA-A Receptor Agonists therapeutic use, Neurons drug effects, Neuropeptides therapeutic use, Peptide Fragments therapeutic use, Receptors, GABA-A drug effects, Stroke drug therapy
- Abstract
Following stroke, the survival of neurons and their ability to reestablish connections is critical to functional recovery. This is strongly influenced by the balance between neuronal excitation and inhibition. In the acute phase of experimental stroke, lethal hyperexcitability can be attenuated by positive allosteric modulation of GABA
A receptors (GABAA Rs). Conversely, in the late phase, negative allosteric modulation of GABAA R can correct the suboptimal excitability and improves both sensory and motor recovery. Here, we hypothesized that octadecaneuropeptide (ODN), an endogenous allosteric modulator of the GABAA R synthesized by astrocytes, influences the outcome of ischemic brain tissue and subsequent functional recovery. We show that ODN boosts the excitability of cortical neurons, which makes it deleterious in the acute phase of stroke. However, if delivered after day 3, ODN is safe and improves motor recovery over the following month in two different paradigms of experimental stroke in mice. Furthermore, we bring evidence that, during the subacute period after stroke, the repairing cortex can be treated with ODN by means of a single hydrogel deposit into the stroke cavity. SIGNIFICANCE STATEMENT Stroke remains a devastating clinical challenge because there is no efficient therapy to either minimize neuronal death with neuroprotective drugs or to enhance spontaneous recovery with neurorepair drugs. Around the brain damage, the peri-infarct cortex can be viewed as a reservoir of plasticity. However, the potential of wiring new circuits in these areas is restrained by a chronic excess of GABAergic inhibition. Here we show that an astrocyte-derived peptide, can be used as a delayed treatment, to safely correct cortical excitability and facilitate sensorimotor recovery after stroke., (Copyright © 2021 the authors.)- Published
- 2021
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13. Point-Substitution of Phenylalanine Residues of 26RFa Neuropeptide: A Structure-Activity Relationship Study.
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Lefranc B, Alim K, Neveu C, Le Marec O, Dubessy C, Boutin JA, Chuquet J, Vaudry D, Prévost G, Picot M, Vaudry H, Chartrel N, and Leprince J
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- Animals, CHO Cells, Cricetulus, Humans, Phenylalanine chemistry, Phenylalanine genetics, Receptors, G-Protein-Coupled metabolism, Structure-Activity Relationship, Amino Acid Substitution, Neuropeptides chemistry, Neuropeptides genetics, Neuropeptides pharmacology, Receptors, G-Protein-Coupled agonists
- Abstract
26RFa is a neuropeptide that activates the rhodopsin-like G protein-coupled receptor QRFPR/GPR103. This peptidergic system is involved in the regulation of a wide array of physiological processes including feeding behavior and glucose homeostasis. Herein, the pharmacological profile of a homogenous library of QRFPR-targeting peptide derivatives was investigated in vitro on human QRFPR-transfected cells with the aim to provide possible insights into the structural determinants of the Phe residues to govern receptor activation. Our work advocates to include in next generations of 26RFa
(20-26) -based QRFPR agonists effective substitutions for each Phe unit, i.e., replacement of the Phe22 residue by a constrained 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid moiety, and substitution of both Phe24 and Phe26 by their para -chloro counterpart. Taken as a whole, this study emphasizes that optimized modifications in the C-terminal part of 26RFa are mandatory to design selective and potent peptide agonists for human QRFPR.- Published
- 2021
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14. Prolonged deficit of low gamma oscillations in the peri-infarct cortex of mice after stroke.
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Hazime M, Alasoadura M, Lamtahri R, Quilichini P, Leprince J, Vaudry D, and Chuquet J
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- Animals, Brain Ischemia pathology, Cerebral Infarction pathology, Male, Mice, Mice, Inbred C57BL, Neocortex pathology, Stroke pathology, Brain Ischemia physiopathology, Cerebral Infarction physiopathology, Gamma Rhythm physiology, Neocortex physiopathology, Stroke physiopathology
- Abstract
Days and weeks after an ischemic stroke, the peri-infarct area adjacent to the necrotic tissue exhibits very intense synaptic reorganization aimed at regaining lost functions. In order to enhance functional recovery, it is important to understand the mechanisms supporting neural repair and neuroplasticity in the cortex surrounding the lesion. Brain oscillations of the local field potential (LFP) are rhythmic fluctuations of neuronal excitability that synchronize neuronal activity to organize information processing and plasticity. Although the oscillatory activity of the brain has been probed after stroke in both animals and humans using electroencephalography (EEG), the latter is ineffective to precisely map the oscillatory changes in the peri-infarct zone where synaptic plasticity potential is high. Here, we worked on the hypothesis that the brain oscillatory system is altered in the surviving peri-infarct cortex, which may slow down the functional repair and reduce the recovery. In order to document the relevance of this hypothesis, oscillatory power was measured at various distances from the necrotic core at 7 and 21 days after a permanent cortical ischemia induced in mice. Delta and theta oscillations remained at a normal power in the peri-infarct cortex, in contrast to low gamma oscillations that displayed a gradual decrease, when approaching the border of the lesion. A broadband increase of power was also observed in the homotopic contralateral sites. Thus, the proximal peri-infarct cortex could become a target of therapeutic interventions applied to correct the oscillatory regimen in order to boost post-stroke functional recovery., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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15. Cytoprotective and Neurotrophic Effects of Octadecaneuropeptide (ODN) in in vitro and in vivo Models of Neurodegenerative Diseases.
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Masmoudi-Kouki O, Namsi A, Hamdi Y, Bahdoudi S, Ghouili I, Chuquet J, Leprince J, Lefranc B, Ghrairi T, Tonon MC, Lizard G, and Vaudry D
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- Animals, Cytoprotection physiology, Humans, Mice, Nerve Growth Factors administration & dosage, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Neuroprotection physiology, Oxidative Stress drug effects, Oxidative Stress physiology, Cytoprotection drug effects, Diazepam Binding Inhibitor administration & dosage, Disease Models, Animal, Neurodegenerative Diseases prevention & control, Neuropeptides administration & dosage, Neuroprotection drug effects, Neuroprotective Agents administration & dosage, Peptide Fragments administration & dosage
- Abstract
Octadecaneuropeptide (ODN) and its precursor diazepam-binding inhibitor (DBI) are peptides belonging to the family of endozepines. Endozepines are exclusively produced by astroglial cells in the central nervous system of mammals, and their release is regulated by stress signals and neuroactive compounds. There is now compelling evidence that the gliopeptide ODN protects cultured neurons and astrocytes from apoptotic cell death induced by various neurotoxic agents. In vivo , ODN causes a very strong neuroprotective action against neuronal degeneration in a mouse model of Parkinson's disease. The neuroprotective activity of ODN is based on its capacity to reduce inflammation, apoptosis, and oxidative stress. The protective effects of ODN are mediated through its metabotropic receptor. This receptor activates a transduction cascade of second messengers to stimulate protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) signaling pathways, which in turn inhibits the expression of proapoptotic factor Bax and the mitochondrial apoptotic pathway. In N2a cells, ODN also promotes survival and stimulates neurite outgrowth. During the ODN-induced neuronal differentiation process, numerous mitochondria and peroxisomes are identified in the neurites and an increase in the amount of cholesterol and fatty acids is observed. The antiapoptotic and neurotrophic properties of ODN, including its antioxidant, antiapoptotic, and pro-differentiating effects, suggest that this gliopeptide and some of its selective and stable derivatives may have therapeutic value for the treatment of some neurodegenerative diseases., (Copyright © 2020 Masmoudi-Kouki, Namsi, Hamdi, Bahdoudi, Ghouili, Chuquet, Leprince, Lefranc, Ghrairi, Tonon, Lizard and Vaudry.)
- Published
- 2020
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16. Endozepines and their receptors: Structure, functions and pathophysiological significance.
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Tonon MC, Vaudry H, Chuquet J, Guillebaud F, Fan J, Masmoudi-Kouki O, Vaudry D, Lanfray D, Morin F, Prevot V, Papadopoulos V, Troadec JD, and Leprince J
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- Animals, Diazepam Binding Inhibitor metabolism, Humans, Benzodiazepines metabolism, Receptors, GABA-A metabolism
- Abstract
The existence of specific binding sites for benzodiazepines (BZs) in the brain has prompted the search for endogenous BZ receptor ligands designated by the generic term « endozepines ». This has led to the identification of an 86-amino acid polypeptide capable of displacing [
3 H]diazepam binding to brain membranes, thus called diazepam-binding inhibitor (DBI). It was subsequently found that the sequence of DBI is identical to that of a lipid carrier protein termed acyl-CoA-binding protein (ACBP). The primary structure of DBI/ACBP has been well preserved, suggesting that endozepines exert vital functions. The DBI/ACBP gene is expressed by astroglial cells in the central nervous system, and by various cell types in peripheral organs. Endoproteolytic cleavage of DBI/ACBP generates several bioactive peptides including a triakontatetraneuropeptide that acts as a selective ligand of peripheral BZ receptors/translocator protein, and an octadecaneuropeptide that activates a G protein-coupled receptor and behaves as an allosteric modulator of the GABAA R. Although DBI/ACBP is devoid of a signal peptide, endozepines are released by astrocytes in a regulated manner. Consistent with the diversity and wide distribution of BZ-binding sites, endozepines appear to exert a large array of biological functions and pharmacological effects. Thus, intracerebroventricular administration of DBI or derived peptides induces proconflict and anxiety-like behaviors, and reduces food intake. Reciprocally, the expression of DBI/ACBP mRNA is regulated by stress and metabolic signals. In vitro, endozepines stimulate astrocyte proliferation and protect neurons and astrocytes from apoptotic cell death. Endozepines also regulate neurosteroid biosynthesis and neuropeptide expression, and promote neurogenesis. In peripheral organs, endozepines activate steroid hormone production, stimulate acyl chain ceramide synthesis and trigger pro-inflammatory cytokine secretion. The expression of the DBI/ACBP gene is enhanced in addiction/withdrawal animal models, in patients with neurodegenerative disorders and in various types of tumors. We review herein the current knowledge concerning the various actions of endozepines and discuss the physiopathological implications of these regulatory gliopeptides., (Copyright © 2019. Published by Elsevier Inc.)- Published
- 2020
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17. Design, Synthesis, Molecular Dynamics Simulation, and Functional Evaluation of a Novel Series of 26RFa Peptide Analogues Containing a Mono- or Polyalkyl Guanidino Arginine Derivative.
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Alim K, Lefranc B, Sopkova-de Oliveira Santos J, Dubessy C, Picot M, Boutin JA, Vaudry H, Chartrel N, Vaudry D, Chuquet J, and Leprince J
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- Alkylation, Amides chemistry, Animals, CHO Cells, Chemistry Techniques, Synthetic, Cricetulus, Protein Conformation, Arginine chemistry, Drug Design, Guanidine chemistry, Molecular Dynamics Simulation, Oligopeptides chemical synthesis, Oligopeptides chemistry
- Abstract
26RFa, the endogenous QRFPR ligand, is implicated in several physiological and pathological conditions such as the regulation of glucose homeostasis and bone mineralization; hence, QRFPR ligands display therapeutic potential. At the molecular level, functional interaction occurs between residues Arg
25 of 26RFa and Gln125 of QRFPR. We have designed 26RFa(20-26) analogues incorporating arginine derivatives modified by alkylated substituents. We found that the Arg25 side chain length was necessary to retain the activity of 26RFa(20-26) and that N-monoalkylation of arginine was accommodated by the QRFPR active site. In particular, [(Me)ω Arg25 ]26RFa(20-26) (5b, LV-2186) appeared to be 25-fold more potent than 26RFa(20-26) and displayed a position in a QRFPR homology model slightly different to that of the unmodified heptapeptide. Other peptides were less potent than 26RFa(20-26) , exhibited partial agonistic activity, or were totally inactive in accordance to different ligand-bound structures. In vivo, [(Me)ω Arg25 ]26RFa(20-26) exerted a delayed 26RFa-like hypoglycemic effect. Finally, N-methyl substituted arginine-containing peptides represent lead compounds for further development of QRFPR agonists.- Published
- 2018
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18. Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson's disease.
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Bahdoudi S, Ghouili I, Hmiden M, do Rego JL, Lefranc B, Leprince J, Chuquet J, do Rego JC, Marcher AB, Mandrup S, Vaudry H, Tonon MC, Amri M, Masmoudi-Kouki O, and Vaudry D
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- Animals, Disease Models, Animal, Dopaminergic Neurons drug effects, Dopaminergic Neurons metabolism, Dopaminergic Neurons pathology, Gene Expression Regulation drug effects, Humans, Male, Mice, Inbred C57BL, Oxidative Stress drug effects, Parkinson Disease genetics, Parkinson Disease metabolism, Parkinson Disease pathology, Reactive Oxygen Species metabolism, Diazepam Binding Inhibitor therapeutic use, Neuropeptides therapeutic use, Neuroprotective Agents therapeutic use, Parkinson Disease drug therapy, Peptide Fragments therapeutic use
- Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine (DA) neurons through apoptotic, inflammatory and oxidative stress mechanisms. The octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. The present study reveals that a single intracerebroventricular injection of 10 ng ODN 1 h after the last administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented the degeneration of DA neurons induced by the toxin in the substantia nigra pars compacta of mice, 7 days after treatment. ODN-mediated neuroprotection was associated with a reduction of the number of glial fibrillary acidic protein-positive reactive astrocytes and a strong inhibition of the expression of pro-inflammatory genes such as interleukins 1β and 6, and tumor necrosis factor-α. Moreover, ODN blocked the inhibition of the anti-apoptotic gene Bcl-2, and the stimulation of the pro-apoptotic genes Bax and caspase-3, induced by MPTP in the substantia nigra pars compacta. ODN also decreased or even in some cases abolished MPTP-induced oxidative damages, overproduction of reactive oxygen species and accumulation of lipid oxidation products in DA neurons. Furthermore, DBI knockout mice appeared to be more vulnerable than wild-type animals to MPTP neurotoxicity. Taken together, these results show that the gliopeptide ODN exerts a potent neuroprotective effect against MPTP-induced degeneration of nigrostriatal DA neurons in mice, through mechanisms involving downregulation of neuroinflammatory, oxidative and apoptotic processes. ODN may, thus, reduce neuronal damages in PD and other cerebral injuries involving oxidative neurodegeneration.
- Published
- 2018
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19. Investigations of octylglyceryl dextran-graft-poly(lactic acid) nanoparticles for peptide delivery to the brain.
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Boussahel A, Ibegbu DM, Lamtahri R, Maucotel J, Chuquet J, Lefranc B, Leprince J, Roldo M, Mével JL, Gorecki D, and Barbu E
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- Animals, Brain diagnostic imaging, Cell Line, Dextrans chemistry, Humans, Mice, Nanoparticles chemistry, Particle Size, Peptides chemistry, Polyesters chemistry, Blood-Brain Barrier drug effects, Brain drug effects, Drug Delivery Systems, Nanoparticles administration & dosage, Peptides administration & dosage
- Abstract
Aim: Develop modified dextran nanoparticles showing potential to assist with drug permeation across the blood-brain barrier for the delivery of neuropeptides., Methods: Nanoparticles loaded by emulsification with model macromolecular actives were characterized in terms of stability, cytotoxicity and drug-release behavior. Peptide-loaded nanoformulations were tested in an in vivo trout model and in food-deprived mice., Results: Nanoformulations loaded with model peptides showed good stability and appeared nontoxic in low concentration against human brain endothelial cells. They were found to preserve the bioactivity of loaded peptides (angiotensin II) as demonstrated in vivo using a trout model, and to induce a transient reduction of food consumption in mice when loaded with an anorexigenic octaneuropeptide., Conclusion: Octylglyceryl dextran-graft-poly(lactic acid) nanoparticles formulated by emulsification demonstrate potential for peptide delivery.
- Published
- 2017
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20. Rational design of a low molecular weight, stable, potent, and long-lasting GPR103 aza-β3-pseudopeptide agonist.
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Neveu C, Lefranc B, Tasseau O, Do-Rego JC, Bourmaud A, Chan P, Bauchat P, Le Marec O, Chuquet J, Guilhaudis L, Boutin JA, Ségalas-Milazzo I, Costentin J, Vaudry H, Baudy-Floc'h M, Vaudry D, and Leprince J
- Subjects
- Animals, Circular Dichroism, Drug Stability, Hydrogen Bonding, Injections, Intraventricular, Male, Mice, Molecular Weight, Peptides administration & dosage, Aza Compounds pharmacology, Drug Design, Feeding Behavior drug effects, Peptides pharmacology, Receptors, G-Protein-Coupled agonists
- Abstract
26RFa, a novel RFamide neuropeptide, is the endogenous ligand of the former orphan receptor GPR103. Intracerebroventricular injection of 26RFa and its C-terminal heptapeptide, 26RFa((20-26)), stimulates food intake in rodents. To develop potent, stable ligands of GPR103 with low molecular weight, we have designed a series of aza-β(3)-containing 26RFa((20-26)) analogues for their propensity to establish intramolecular hydrogen bonds, and we have evaluated their ability to increase [Ca(2+)](i) in GPR103-transfected cells. We have identified a compound, [Cmpi(21),aza-β(3)-Hht(23)]26RFa((21-26)), which was 8-fold more potent than 26RFa((20-26)) in mobilizing [Ca(2+)](i). This pseudopeptide was more stable in serum than 26RFa((20-26)) and exerted a longer lasting orexigenic effect in mice. This study constitutes an important step toward the development of 26RFa analogues that could prove useful for the treatment of feeding disorders.
- Published
- 2012
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21. Local Ca2+ detection and modulation of synaptic release by astrocytes.
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Di Castro MA, Chuquet J, Liaudet N, Bhaukaurally K, Santello M, Bouvier D, Tiret P, and Volterra A
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- Action Potentials drug effects, Action Potentials physiology, Adenosine Diphosphate analogs & derivatives, Adenosine Diphosphate pharmacology, Animals, Animals, Newborn, Astrocytes drug effects, Astrocytes ultrastructure, Biophysics, Calcium Signaling drug effects, Cell Communication drug effects, Cell Communication physiology, Chelating Agents pharmacology, Egtazic Acid analogs & derivatives, Egtazic Acid pharmacology, Electric Stimulation methods, Enzyme Inhibitors pharmacology, Gene Expression Regulation drug effects, Gene Expression Regulation genetics, Heparin pharmacology, Hippocampus cytology, In Vitro Techniques, Inositol 1,4,5-Trisphosphate Receptors deficiency, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Biological, Patch-Clamp Techniques, Purinergic P2Y Receptor Antagonists pharmacology, Sodium Channel Blockers pharmacology, Sucrose pharmacology, Synapses drug effects, Synaptic Transmission drug effects, Synaptic Transmission physiology, Tetrodotoxin pharmacology, Thapsigargin pharmacology, Astrocytes physiology, Calcium metabolism, Calcium Signaling physiology, Synapses metabolism
- Abstract
Astrocytes communicate with synapses by means of intracellular calcium ([Ca(2+)](i)) elevations, but local calcium dynamics in astrocytic processes have never been thoroughly investigated. By taking advantage of high-resolution two-photon microscopy, we identify the characteristics of local astrocyte calcium activity in the adult mouse hippocampus. Astrocytic processes showed intense activity, triggered by physiological transmission at neighboring synapses. They encoded synchronous synaptic events generated by sparse action potentials into robust regional (∼12 μm) [Ca(2+)](i) elevations. Unexpectedly, they also sensed spontaneous synaptic events, producing highly confined (∼4 μm), fast (millisecond-scale) miniature Ca(2+) responses. This Ca(2+) activity in astrocytic processes is generated through GTP- and inositol-1,4,5-trisphosphate-dependent signaling and is relevant for basal synaptic function. Thus, buffering astrocyte [Ca(2+)](i) or blocking a receptor mediating local astrocyte Ca(2+) signals decreased synaptic transmission reliability in minimal stimulation experiments. These data provide direct evidence that astrocytes are integrated in local synaptic functioning in adult brain., (© 2011 Nature America, Inc. All rights reserved.)
- Published
- 2011
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22. Predominant enhancement of glucose uptake in astrocytes versus neurons during activation of the somatosensory cortex.
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Chuquet J, Quilichini P, Nimchinsky EA, and Buzsáki G
- Subjects
- Analysis of Variance, Animals, Biological Transport, Male, Microscopy, Fluorescence, Multiphoton, Rats, Rats, Sprague-Dawley, Vibrissae physiology, Astrocytes metabolism, Glucose metabolism, Neurons metabolism, Somatosensory Cortex metabolism
- Abstract
Glucose is the primary energetic substrate of the brain, and measurements of its metabolism are the basis of major functional cerebral imaging methods. Contrary to the general view that neurons are fueled solely by glucose in proportion to their energetic needs, recent in vitro and ex vivo analyses suggest that glucose preferentially feeds astrocytes. However, the cellular fate of glucose in the intact brain has not yet been directly observed. We have used a real-time method for measuring glucose uptake in astrocytes and neurons in vivo in male rats by imaging the trafficking of the nonmetabolizable glucose analog 6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-aminoglucose (6-NBDG) using two-photon microscopy. During resting conditions we found that astrocytes and neurons both take up 6-NBDG at the same rate in the barrel cortex of the rat. However, during intense neuronal activity triggered by whisker stimulation, astrocytes rapidly accelerated their uptake, whereas neuronal uptake remained almost unchanged. After the stimulation period, astrocytes returned to their preactivation rates of uptake paralleling the neuronal rate of uptake. These observations suggest that glucose is taken up primarily by astrocytes, supporting the view that functional imaging experiments based on glucose analogs extraction may predominantly reflect the metabolic activity of the astrocytic network.
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- 2010
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23. Effects of urotensin-II on cerebral blood flow and ischemia in anesthetized rats.
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Chuquet J, Lecrux C, Chatenet D, Leprince J, Chazalviel L, Roussel S, MacKenzie ET, Vaudry H, and Touzani O
- Subjects
- Analysis of Variance, Animals, Blood Pressure drug effects, Brain Infarction etiology, Brain Infarction prevention & control, Disease Models, Animal, Ischemia physiopathology, Laser-Doppler Flowmetry methods, Male, Rats, Rats, Sprague-Dawley, Time Factors, Anesthesia, Cerebrovascular Circulation drug effects, Ischemia drug therapy, Urotensins therapeutic use
- Abstract
Urotensin-II (U-II) is a cyclic peptide identified recently in many mammalian species including man. U-II and its receptor are expressed in the central nervous system, in the cardiovascular system and in other peripheral tissues. Although this peptide has been reported initially to be a potent vasoconstrictor, increasing evidence shows that its vascular actions strongly depend on species and vascular beds. Here we analyzed the effects of U-II administration on cerebral blood flow (CBF) under physiological conditions and following cerebral ischemia in rats. Although intravenous injection of U-II had minimal effects on CBF as measured by the technique of laser Doppler flowmetry, its administration (10 nmol) into the lateral cerebral ventricle induced gradual and long lasting increase in CBF (+61% at 1 h post-injection, p<0.05). These U-II-mediated CBF increases were not related to the transient systemic pressor actions of the peptide and were reduced by nitric oxide synthase inhibition (61 vs 17%, p<0.05). Intracerebroventricular administration of U-II following the induction of cerebral ischemia, failed to alter residual CBF in the affected cerebral hemisphere. Nonetheless, following reperfusion (90 min after ischemia), U-II-treated animals displayed a remarkable hyperperfusion compared to vehicle-treated rats (+168%, p<0.05). The volume of infarction was significantly increased in U-II-treated rats (+40%, p<0.05). These results provide the first evidence that U-II increases cerebral blood flow when administered into the cerebral ventricle and exacerbates brain damage following an ischemic insult.
- Published
- 2008
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- View/download PDF
24. Spontaneously hypertensive rats are highly vulnerable to AMPA-induced brain lesions.
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Lecrux C, Nicole O, Chazalviel L, Catone C, Chuquet J, MacKenzie ET, and Touzani O
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- Animals, Blood Pressure drug effects, Blood Pressure physiology, Brain Damage, Chronic genetics, Brain Ischemia genetics, Brain Ischemia metabolism, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Cell Death drug effects, Cell Death genetics, Genetic Predisposition to Disease genetics, Hypertension genetics, Hypertension physiopathology, Ion Channel Gating drug effects, Ion Channel Gating physiology, Male, Membrane Potentials drug effects, Membrane Potentials physiology, Nerve Degeneration chemically induced, Nerve Degeneration metabolism, Nerve Degeneration physiopathology, Neurotoxins toxicity, Phosphorylation drug effects, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Receptors, AMPA agonists, Regional Blood Flow drug effects, Regional Blood Flow physiology, Vascular Resistance drug effects, Vascular Resistance physiology, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid toxicity, Brain Damage, Chronic etiology, Brain Damage, Chronic physiopathology, Brain Ischemia physiopathology, Glutamic Acid metabolism, Hypertension complications, Receptors, AMPA metabolism
- Abstract
Background and Purpose: Whereas the effects of chronic arterial hypertension on the cerebral vasculature have been widely studied, its effects on brain tissue have been studied less so. Here we examined if spontaneously hypertensive rats (SHRs) or the normotensive control Wistar Kyoto rats (WKYs) made hypertensive by renal artery stenosis (R-WKYs) are vulnerable to an excitotoxic brain lesion provoked by an overactivation of glutamate receptors., Methods: Lesion volumes were quantified by histology in WKYs and SHRs subjected to striatal administration of N-methyl-d-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). The expression of AMPA receptors subunits and calcium/calmodulin kinase-II alpha was analyzed by real-time polymerase chain reaction and Western blot., Results: NMDA (50 and 75 nmol) induced similar lesions in both SHRs (10+/-2 mm(3) and 16+/-4 mm(3), respectively) and WKYs (11+/-2 mm(3) and 19+/-7 mm(3), respectively). However, AMPA-induced (2.5 and 5 nmol) lesions were significantly greater in 14-week-old SHRs (14+/-3 mm(3) and 20+/-5 mm(3), respectively) than WKYs (4+/-2 mm(3), P<0.05 and 7+/-4 mm(3), P<0.001, respectively). Furthermore, normotensive 7-week-old SHRs also displayed an aggravated AMPA-induced lesion compared with age-matched WKYs (10+/-3 mm(3) vs 6+/-3 mm(3); P<0.05). Neither NMDA nor AMPA produced increased lesion volumes in R-WKYs (12+/-3 mm(3) and 5+/-4 mm(3), respectively) compared with WKYs. Striatal levels of AMPA receptors subunits, GluR1 and GluR2, were not different between SHRs and WKYs. However, SHRs displayed an increase in phosphorylated form of GluR1 at Ser-831 (P<0.05), as well as in calcium/calmodulin kinase-II alpha (P<0.002). Selective inhibition of this kinase by KN-93 reduced AMPA-induced damage in SHRs (P<0.01 vs vehicle)., Conclusions: These findings show that an increase in phosphorylated GluR1, which increases AMPA receptor conductance, may be involved in the vulnerability of SHRs to AMPA.
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- 2007
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- View/download PDF
25. High-resolution in vivo imaging of the neurovascular unit during spreading depression.
- Author
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Chuquet J, Hollender L, and Nimchinsky EA
- Subjects
- Animals, Astrocytes cytology, Astrocytes physiology, Blood Flow Velocity physiology, Cerebral Cortex cytology, Microscopy, Confocal methods, Neurons cytology, Rats, Rats, Sprague-Dawley, Cerebral Cortex blood supply, Cerebral Cortex physiology, Cortical Spreading Depression physiology, Neurons physiology
- Abstract
Spreading depression (SD) is a propagating wave of neuronal depolarization and ionic shifts, seen in stroke and migraine. In vitro, SD is associated with astrocytic [Ca2+] waves, but it is unclear what role they play and whether they influence cerebral blood flow, which is altered in SD. Here we show that SD in vivo is associated with [Ca2+] waves in astrocytes and neurons and with constriction of intracortical arterioles severe enough to result in arrest of capillary perfusion. The vasoconstriction is correlated with fast astrocytic [Ca2+] waves and is inhibited when they are reduced. [Ca2+] waves appear in neurons before astrocytes, and inhibition of astrocytic [Ca2+] waves does not depress SD propagation. This suggests that astrocytes do not drive SD propagation but are responsible for the hemodynamic failure seen deep in the cortex. Similar waves occur in anoxic depolarizations (AD), supporting the notion that SD and AD are related processes.
- Published
- 2007
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- View/download PDF
26. Selective blockade of endothelin-B receptors exacerbates ischemic brain damage in the rat.
- Author
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Chuquet J, Benchenane K, Toutain J, MacKenzie ET, Roussel S, and Touzani O
- Subjects
- Animals, Antihypertensive Agents administration & dosage, Blood Flow Velocity drug effects, Brain Ischemia chemically induced, Cerebrovascular Circulation drug effects, Disease Models, Animal, Excitatory Amino Acid Agonists administration & dosage, Excitatory Amino Acid Agonists toxicity, Gene Expression drug effects, Infarction, Middle Cerebral Artery pathology, Injections, Intraventricular, Male, N-Methylaspartate administration & dosage, N-Methylaspartate toxicity, Oligopeptides administration & dosage, Piperidines administration & dosage, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Receptor, Endothelin B, Receptors, Endothelin genetics, Antihypertensive Agents adverse effects, Brain Ischemia pathology, Endothelin Receptor Antagonists, Oligopeptides adverse effects, Piperidines adverse effects
- Abstract
Background and Purpose: Endothelins act through 2 receptors, namely, ET(A) and ET(B). In the cerebral circulation, ET(A) mediates marked and prolonged vasoconstriction, and its blockade increases cerebral blood flow (CBF) and reduces ischemic brain damage. However, the role of ET(B) receptors remains unclear. In this study we examined, in rats, the kinetics of expression of ET(B) and the effects of ET(B) blockade on changes in CBF and brain damage after focal cerebral ischemia and N-methyl-D-aspartate (NMDA)-induced excitotoxic injury., Methods: Rats were subjected to transient (60 minutes) focal cerebral ischemia or cortical injection of NMDA. The selective ET(B) antagonist BQ-788 was injected intracerebroventricularly 30 minutes before and 30 minutes after the onset of ischemia. Cortical perfusion was monitored by laser-Doppler flowmetry. The volume of infarction or NMDA-induced cortical lesion was assessed at 24 hours after the insult. The reverse transcription-polymerase chain reaction technique was used to assess ET(B) expression., Results: Cerebral ischemia failed to alter the expression of ET(B) mRNA in both acute and chronic stages. Administration of BQ-788 resulted in an increase in infarction volume (178%; P<0.05) accompanied by a decrease in residual CBF (-26.7% versus control; P<0.01). In these animals we found a positive correlation between the volume of infarction and the severity of the decrease in CBF. NMDA-induced cortical lesions were not affected by the administration of BQ-788., Conclusions: Our results suggest that the ET(B) antagonist BQ-788 induces deleterious effects that are mediated by the reduction of residual blood flow after ischemia and argue that the optimal therapeutic strategy in stroke would be to target the use of selective ET(A) antagonists and not mixed ET(A)/ET(B) antagonists.
- Published
- 2002
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27. Matching gene expression with hypometabolism after cerebral ischemia in the nonhuman primate.
- Author
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Chuquet J, Benchenane K, Liot G, Fernández-Monreal M, Toutain J, Blanchet S, Eveno E, Auffray C, Piétu G, Buisson A, Touzani O, MacKenzie ET, and Vivien D
- Subjects
- Animals, Brain blood supply, Brain Ischemia metabolism, Cerebral Arteries metabolism, Cerebral Arteries pathology, Cloning, Molecular, Cluster Analysis, DNA, Complementary, Disease Models, Animal, Male, Oligonucleotide Array Sequence Analysis, Oxygen Consumption, Papio, Brain metabolism, Brain Ischemia genetics, Gene Expression Regulation
- Abstract
To correlate brain metabolic status with the molecular events during cerebral ischemia, a cDNA array was performed after positron emission tomography scanning in a model of focal cerebral ischemia in baboons. Cluster analysis for the expression of 74 genes allowed the identification of 4 groups of genes. In each of the distinct groups, the authors observed a marked inflection in the pattern of gene expression when the CMRo was reduced by 48% to 66%. These patterns of coordinated modifications in gene expression could define molecular checkpoints for the development of an ischemic infarct and a molecular definition of the penumbra.
- Published
- 2002
- Full Text
- View/download PDF
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