Erythropoietin and Its Derivates Modulate Mitochondrial Dysfunction after Diffuse Traumatic Brain Injury
| العنوان: | Erythropoietin and Its Derivates Modulate Mitochondrial Dysfunction after Diffuse Traumatic Brain Injury |
|---|---|
| المؤلفون: | Karin Pernet-Gallay, Jean François Payen, Pierre Bouzat, Thibaut Trouve-Buisson, Anne Millet, Cécile Batandier, Lucie Gaide-Chevronnay, Eric Fontaine, Thierry Debillon, Emmanuel L. Barbier |
| المساهمون: | INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Réanimation Pédiatrique, Hôpital Couple-Enfant-Hôpital Couple-Enfant, ANTE-INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, Pôle Anesthésie Réanimation, CHU Grenoble-Hôpital Michallon-CHU Grenoble-Hôpital Michallon, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Registre des Handicaps de l'Enfant et Observatoire Périnatal Isère, RHEOP, Centre Hospitalier Universitaire [Grenoble] (CHU), CIC - Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Anesthésie Réanimation |
| المصدر: | Journal of Neurotrauma Journal of Neurotrauma, Mary Ann Liebert, 2016, 33 (17), pp.1625-1633. ⟨10.1089/neu.2015.4160⟩ |
| بيانات النشر: | HAL CCSD, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Traumatic brain injury, [SDV]Life Sciences [q-bio], Pharmacology, Mitochondrion, Mitochondrial Membrane Transport Proteins, 03 medical and health sciences, Mitochondrial membrane transport protein, chemistry.chemical_compound, 0302 clinical medicine, Brain Injuries, Traumatic, Medicine, Animals, Humans, Rats, Wistar, Erythropoietin, ComputingMilieux_MISCELLANEOUS, Calcium metabolism, biology, business.industry, Mitochondrial Permeability Transition Pore, MPTP, medicine.disease, nervous system diseases, Mitochondria, Rats, 030104 developmental biology, Neuroprotective Agents, nervous system, Mitochondrial permeability transition pore, chemistry, Apoptosis, Anesthesia, biology.protein, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | Inhibiting the opening of mitochondrial permeability transition pore (mPTP), thereby maintaining the mitochondrial membrane potential and calcium homeostasis, could reduce the induction of cell death. Although recombinant human erythropoietin (rhEpo) and carbamylated erythropoietin (Cepo) were shown to prevent apoptosis after traumatic brain injury (TBI), their impact on mPTP is yet unknown. Thirty minutes after diffuse TBI (impact-acceleration model), rats were intravenously administered a saline solution (TBI-saline), 5000 UI/kg rhEpo (TBI-rhEpo) or 50 μg/kg Cepo (TBI-Cepo). A fourth group received no TBI insult (sham-operated) (n = 11 rats per group). Post-traumatic brain edema was measured using magnetic resonance imaging. A first series of experiments was conducted 2 h after TBI (or equivalent) to investigate the mitochondrial function with the determination of thresholds for mPTP opening and ultrastructural mitochondrial changes. In addition, the intramitochondrial calcium content [Caim] was measured. In a second series of experiments, brain cell apoptosis was assessed at 24 h post-injury. TBI-rhEpo and TBI-Cepo groups had a reduced brain edema compared with TBI-saline. They had higher threshold for mPTP opening with succinate as substrate: 120 (120-150) (median, interquartiles) and 100 (100-120) versus 80 (60-90) nmol calcium/mg protein in TBI-saline, respectively (p 0.05). Similar findings were shown with glutamate-malate as substrate. TBI-rhEpo and Cepo groups had less morphological mitochondrial disruption in astrocytes. The elevation in [Caim] after TBI was not changed by rhEpo and Cepo treatment. Finally, rhEpo and Cepo reduced caspase-3 expression at 24 h post-injury. These results indicate that rhEpo and Cepo could modulate mitochondrial dysfunction after TBI. The mechanisms involved are discussed. |
| اللغة: | English |
| تدمد: | 0897-7151 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1addc99c2fe04686fe42491f2d7ab811 https://hal.univ-grenoble-alpes.fr/hal-01930835 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....1addc99c2fe04686fe42491f2d7ab811 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 08977151 |
|---|