Catabolic signaling and muscle wasting after acute ischemic stroke in mice: Indication for a stroke-specific sarcopenia

Jochen Springer, Susanne Schust, Katrin Peske, Anika Tschirner, Andre Rex, Odilo Engel, Nadja Scherbakov, Andreas Meisel, Stephan Von Haehling, Michael Boschmann, Stefan D. Anker, Ulrich Dirnagl, Wolfram Doehner

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3675-3683
Number of pages9
JournalStroke
Volume45
Issue number12
DOIs
Publication statusPublished - Dec 11 2014

Keywords

  • Cachexia
  • Muscles
  • Sarcopenia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialised Nursing
  • Medicine(all)

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