Elevated tumor necrosis factor-alpha in skeletal muscle after stroke.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha), 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-alpha expression in hemiparetic skeletal muscle. This study investigates whether TNF-alpha mRNA levels are elevated in paretic compared with nonparetic leg muscles of chronic ischemic stroke patients and age-matched controls.


METHODS
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-alpha transcripts were amplified by real-time quantitative polymerase chain reaction. TNF-alpha mRNA concentrations were normalized against acidic ribosomal phosphoprotein, housekeeping gene.


RESULTS
TNF-alpha 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-alpha mRNA in paretic compared with nonparetic leg.


CONCLUSIONS
Findings demonstrate increased TNF-alpha expression in paretic leg muscle, suggesting inflammatory pathways are accelerated in stroke muscle. Further studies are under way to determine whether intramuscular TNF-alpha contributes to atrophy and metabolic abnormalities after stroke.
Hafer-Macko
Charlene E
CE
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. cmacko@grecc.umaryland.edu
Yu
Shuzhen
S
Ryan
Alice S
AS
Ivey
Frederick M
FM
Macko
Richard F
RF
D000368:Aged; D001284:Atrophy / Q000473:pathology; D016022:Case-Control Studies; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007866:Leg / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012270:Ribosomes / Q000737:chemistry; D020521:Stroke / Q000378:metabolism* / Q000473:pathology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D018076:DNA, Complementary; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D012313:RNA