1. Muscle Injury Induces Postoperative Cognitive Dysfunction
- Author
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Grégory Jouvion, Lorna Guéniot, Fabrice Chrétien, Anne Danckaert, Olivier Langeron, Victoria Lepere, Gabriela Ferreira de Medeiros, Marine Le Dudal, Patricia Flamant, Pierre L. Goossens, Neuropathologie expérimentale - Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5), Direction Générale de l'Armement [Paris] (DGA), Ministère des armées, École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Institut Pasteur [Paris] (IP), Department of Anesthesia and Critical Care [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil]-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Neuropathologie [Paris], Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-GHU Paris Psychiatrie et Neurosciences, CHU Trousseau [APHP], Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This work was supported by the Fondation des Gueules Cassées. Lorna Guéniot received financial support from DGA (Direction Générale de l’Armement, France) and Institut Pasteur of Paris for the realization of her PhD. The PBI-Utech is part of the France BioImaging infrastructure supported by the French National Research Agency (ANR-10-INSB-04-01, 'Investments for the future') and is grateful for the support from the Conseil de la Region Ile-de-France (program Sesame 2007, project Imagopole, S.L. Shorte)., Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 (UPD5), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED BioSPC), Université Sorbonne Paris Cité (USPC)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), UF de Génétique chromosomique [CHU Trousseau], and Bodescot, Myriam
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Male ,Aging ,[SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery ,[SDV]Life Sciences [q-bio] ,Neuroimmunology ,Hippocampus ,lcsh:Medicine ,Bioinformatics ,Mice ,[SCCO]Cognitive science ,0302 clinical medicine ,Postoperative Complications ,030202 anesthesiology ,Nerve Growth Factor ,Medicine ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,Brain ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Cytokines ,Microglia ,medicine.symptom ,CX3C Chemokine Receptor 1 ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,Article ,Lesion ,03 medical and health sciences ,Postoperative Cognitive Complications ,Animals ,Humans ,Muscle, Skeletal ,Neuroinflammation ,030304 developmental biology ,Brain-derived neurotrophic factor ,business.industry ,Brain-Derived Neurotrophic Factor ,lcsh:R ,Skeletal muscle ,[SCCO] Cognitive science ,medicine.disease ,Disease Models, Animal ,Nerve growth factor ,Synaptic plasticity ,lcsh:Q ,business ,Postoperative cognitive dysfunction ,Neurological disorders - Abstract
Postoperative cognitive dysfunction (POCD) is a major complication affecting patients of any age undergoing surgery. This syndrome impacts everyday life up to months after hospital discharge, and its pathophysiology still remains unclear. Translational research focusing on POCD is based on a wide variety of rodent models, such as the murine tibial fracture, whose severity can limit mouse locomotion and proper behavioral assessment. Besides, influence of skeletal muscle injury, a lesion encountered in a wide range of surgeries, has not been explored in POCD occurrence. We propose a physical model of muscle injury in CX3CR1GFP/+ mice (displaying green fluorescent microglial cells) to study POCD, with morphological, behavioral and molecular approaches. We highlighted: alteration of short- and long-term memory after muscle regeneration, wide microglial reactivity in the brain, including hippocampus area, 24 hours after muscle injury, and an alteration of central brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) balance, 28 days after muscle injury. Our results suggest for the first time that muscle injury can have early as well as late impacts on the brain. Our CX3CR1GFP/+ model can also facilitate microglial investigation, more specifically their pivotal role in neuroinflammation and synaptic plasticity, in the pathophysiology of POCD.
- Published
- 2020
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