title: Catabolic signaling and muscle wasting after acute ischemic stroke in mice: indication for a stroke-specific sarcopenia.
abstract: OBJECTIVE
  Muscle wasting is a common complication accompanying stroke. Although it is known to impair poststroke recovery, the mechanisms of subacute catabolism after stroke have not been investigated in detail. The aim of this study is to investigate mechanisms of local and systemic catabolism and muscle wasting (sarcopenia) in a model of ischemic stroke systematically.
  
  
  METHODS
  Changes in body composition and catabolic activation in muscle tissue were studied in a mouse model of acute cerebral ischemia (temporal occlusion of the middle cerebral artery). Tissue wasting (nuclear magnetic resonance spectroscopy), tissue catabolism (caspases-3 and -6, myostatin), and proteasome activity were assessed. Food intake, activity levels, and energy expenditure were assessed, and putative mechanisms of postischemic wasting were tested with appropriate interventions.
  
  
  RESULTS
  Severe weight loss in stroke animals (day 3: weight loss, -21.7%) encompassed wasting of muscle (-12%; skeletal and myocardium) and fat tissue (-27%). Catabolic signaling and proteasome activity were higher in stroke animals in the contralateral and in the ipsilateral leg. Cerebral infarct severity correlated with catabolic activity only in the contralateral leg but not in the ipsilateral leg. Lower energy expenditure in stroke animals together with normal food intake and activity levels suggests compensatory mechanisms to regain weight. Interventions (high caloric feeding, β-receptor blockade, and antibiotic treatment) failed to prevent proteolytic activation and muscle wasting.
  
  
  CONCLUSIONS
  Catabolic pathways of muscle tissue are activated after stroke. Impaired feeding, sympathetic overactivation, or infection cannot fully explain this catabolic activation. Wasting of the target muscle of the disrupted innervation correlated to severity of brain injury. Our data indicate the presence of a stroke-specific sarcopenia.
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Jochen
authors.initials: J
authors.lastname: Springer
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Susanne
authors.initials: S
authors.lastname: Schust
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Katrin
authors.initials: K
authors.lastname: Peske
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Anika
authors.initials: A
authors.lastname: Tschirner
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Andre
authors.initials: A
authors.lastname: Rex
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Odilo
authors.initials: O
authors.lastname: Engel
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Nadja
authors.initials: N
authors.lastname: Scherbakov
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Meisel
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Michael
authors.initials: M
authors.lastname: Boschmann
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.affiliation: From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.). wolfram.doehner@charite.de.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D055948:Sarcopenia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000150:complications* / Q000378:metabolism* / Q000473:pathology
keywords: cachexia; muscles; sarcopenia