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(Stroke. 2005;36:2021.)
© 2005 American Heart Association, Inc.

Research Reports

Elevated Tumor Necrosis Factor- in Skeletal Muscle After Stroke

Charlene E. Hafer-Macko, MD; Shuzhen Yu, MD; Alice S. Ryan, PhD; Frederick M. Ivey, PhD Richard F. Macko, MD

From the University of Maryland School of Medicine Departments of Neurology (C.E.H.-M., S.Y., R.F.M.) and Medicine Geriatrics Division (A.S.R., F.M.I., R.F.M.), Baltimore Veterans Administration Medical Center, Maryland; and Geriatrics Research Education Clinical Center (C.E.H.-M., S.Y., A.S.R., F.M.I., R.F.M.), Baltimore, Md.

Correspondence to Charlene Hafer-Macko, MD, University of Maryland School of Medicine, Department of Neurology, N4W46, 22 S Greene St, Baltimore, MD 21201. E-mail cmacko{at}grecc.umaryland.edu

Background and Purpose— Tumor necrosis factor- (TNF-), an inflammatory cytokine negligibly expressed in normal muscle, is elevated in selected metabolic conditions characterized by muscle wasting and insulin resistance. Inflammation is fundamental to stroke pathogenesis. Stroke patients have gross muscular atrophy and high prevalence of diabetes and insulin resistance. Yet, no previous studies examined TNF- expression in hemiparetic skeletal muscle. This study investigates whether TNF- mRNA levels are elevated in paretic compared with nonparetic leg muscles of chronic ischemic stroke patients and age-matched controls.

Method— Total RNA extracted from bilateral vastus lateralis muscle biopsies from n=20 hemiparetic stroke patients and n=9 healthy controls was reverse transcribed to cDNA, then TNF- transcripts were amplified by real-time quantitative polymerase chain reaction. TNF- mRNA concentrations were normalized against acidic ribosomal phosphoprotein, housekeeping gene.

Results— TNF- mRNA levels were 2.8-fold higher in paretic compared with control leg muscle (6.28±1.86 versus 2.28±0.67; P<0.03) and 1.6-fold higher in nonparetic leg (3.71±1.02; P<0.11) compared with controls. There was a trend for higher TNF- mRNA in paretic compared with nonparetic leg.

Conclusions— Findings demonstrate increased TNF- expression in paretic leg muscle, suggesting inflammatory pathways are accelerated in stroke muscle. Further studies are under way to determine whether intramuscular TNF- contributes to atrophy and metabolic abnormalities after stroke.

Key Words: inflammation • insulin • stroke • tumor necrosis factor

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