Inhibition of inducible nitric oxide synthase reduces an acute peripheral motor neuropathy produced by dermal burn injury in mice.
The systemic inflammatory response produced by a full-thickness dermal burn injury is associated with a peripheral motor neuropathy. We previously reported that a 20% body surface area (BSA) full-thickness dermal burn in C57BL6 mice produced structural and functional deficits in motor axons at a distance from the burn site. The etiology of the neuropathy, however, is not well characterized. Burn injury leads to an increase in production of a number of proinflammatory mediators, including nitric oxide (NO). We tested the hypothesis that dermal burn-induced motor neuropathy is mediated by increased production of NO. NO synthase (NOS) activity was inhibited following a 20% BSA full-thickness burn by injection of non-specific NOS inhibitor, nitro-L-arginine methyl ester or inducible NOS (iNOS) inhibitors, L-N6-(1-iminoethyl) lysine, and aminoguanidine. NOS inhibitors also prevented the reduction in ventral roots mean axon caliber and the decrease in a motor nerve conduction velocity (MCV) following burn. iNOS knockout mice prevented MCV decrease in the first 3 days post-burn, but iNOS knockout MCV was significantly reduced at 7-14 days post-burn. These results suggest that an increase in NO production generated by systemic inflammatory response pathways after burn injury contributes to the development of structural and functional deficits in peripheral motor axons.
Higashimori
Haruki
H
Department of Neurobiology and Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Whetzel
Thomas P
TP
Carlsen
Richard C
RC
D000818:Animals; D002056:Burns / Q000150:complications / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000097:blood; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000473:pathology; D013979:Tibial Nerve / Q000503:physiopathology
D004791:Enzyme Inhibitors; D009573:Nitrites; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II