The extent of cytokine induction in peripheral nerve lesions depends on the mode of injury and NMDA receptor signaling.
We compared cytokine and chemokine induction in mice after sciatic nerve crush and chronic constriction injury (CCI) by quantitative reverse transcriptase polymerase chain reaction. In both nerve lesion paradigms, transcripts for tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, and monocyte chemoattractant protein-1 (MCP-1) were significantly increased in degenerating nerve stumps already at day 1, with a greater magnitude and longer duration in CCI. NMDA receptor blockade significantly reduced cytokine expression after CCI on the mRNA and protein level. In dorsal root ganglia, only IL-10 mRNA levels were modified after nerve injury. Our study indicates that the mode of nerve injury influences the extent of cytokine expression, and identifies NMDA-mediated signaling as one mechanism of cytokine induction in peripheral nerves.
Kleinschnitz
C
C
Department of Neurology, Julius-Maximilians Universität, Josef-Schneider-Str. 11, D-97080, Würzburg, Germany.
Brinkhoff
J
J
Zelenka
M
M
Sommer
C
C
Stoll
G
G
D000704:Analysis of Variance; D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003250:Constriction; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009409:Nerve Crush / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020426:Sciatic Neuropathy / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D018925:Chemokines; D016207:Cytokines; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate