Published Online
on August 18, 2005

A more recent version of this article appeared on September 1, 2005

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Submitted on May 4, 2005
Accepted on May 31, 2005

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; and 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.

^* To whom correspondence should be addressed. 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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