Jochen Springer1, Susanne Schust1, Katrin Peske1, Anika Tschirner1, Andre Rex1, Odilo Engel1, Nadja Scherbakov1, Andreas Meisel1, Stephan von Haehling1, Michael Boschmann1, Stefan D Anker1, Ulrich Dirnagl1, Wolfram Doehner2. 1. 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.). 2. 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.
Abstract
BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: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: Eva Baranovicova; Marian Grendar; Dagmar Kalenska; Anna Tomascova; Daniel Cierny; Jan Lehotsky Journal: J Physiol Biochem Date: 2018-05-11 Impact factor: 4.158
Authors: Maria H H Balch; Hallie Harris; Deepti Chugh; Surya Gnyawali; Cameron Rink; Shahid M Nimjee; W David Arnold Journal: Exp Neurol Date: 2021-05-25 Impact factor: 5.620