Effect of rhTNF-alpha injection into rat sciatic nerve.
To assess whether TNF-alpha causes inflammatory demyelination or axonal degeneration, we injected into rat sciatic nerve saline, 100 U and 1000 U of rhTNF-alpha and studied the electrophysiological and pathological effects. At day 1 electrophysiology showed a slight reduction of proximal compound muscle action potential amplitude and pathology showed edema, inflammatory infiltration of vessel walls and endoneurium only in nerves injected with 1000 U of rhTNF-alpha. At day 5, there was no demyelination and a percentage of degenerated fibers similar in the three groups. To study the blood-nerve barrier, fluorescein isothiocyanate-labelled albumin was given intravenously after intraneural injection. The nerves injected with 1000 U rhTNF-alpha showed a leakage of the tracer in the endoneurium. TNF-alpha does not appear, at the doses used, to have myelinotoxic or axonopathic properties. The electrophysiological effect at day 1 may be due to mechanical compression of nerve fibers as a result of the blood-nerve barrier damage with consequent endoneurial edema.
Uncini
A
A
Center for Neuromuscular Diseases, University of Chieti, Italy. uncini@unich.it
Di Muzio
A
A
Di Guglielmo
G
G
De Angelis
M V
MV
De Luca
G
G
Lugaresi
A
A
Gambi
D
D
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D004487:Edema / Q000276:immunology / Q000473:pathology; D004594:Electrophysiology; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008845:Microinjections; D009410:Nerve Degeneration / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013979:Tibial Nerve / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005456:Fluorescent Dyes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016650:Fluorescein-5-isothiocyanate