Topical application of TNF-alpha antiserum attenuates spinal cord trauma induced edema formation, microvascular permeability disturbances and cell injury in the rat.
The possibility that antiserum to tumour necrosis factor-alpha (TNF-alpha) is neuroprotective in spinal cord injury (SCI) was examined in a rat model. SCI was produced by making an incision into the right dorsal horn at the T10-11 segments. Top TNF-alpha antiserum at three concentrations (1:10; 1:50 and 1:100) given 30 min before or 2 min, 5 min or 10 min after trauma resulted in marked reduction in visible swelling, edema formation, and leakage of radiolabelled iodine tracer within the T9 and T12 segments at 5 h in a dose dependent manner. This neuroprotective effect was most pronounced when the antiserum at the highest dose level (1:10) was applied 10 min after SCI. The TNF-alpha antiserum also reduced the SCI induced upregulation of neuronal nitric oxide synthase (nNOS) immunoreactivity in a concentration dependent manner. Taken together, these results suggest that local application of TNF-alpha antiserum is neuroprotective in SCI and that this effect is mediated through NOS regulation.
Sharma
H S
HS
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. Sharma@medcellbiol.uu.se
Winkler
T
T
Stålberg
E
E
Gordh
T
T
Alm
P
P
Westman
J
J
D000287:Administration, Topical; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000209:etiology / Q000517:prevention & control*; D007106:Immune Sera / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply; D013118:Spinal Cord Diseases / Q000209:etiology / Q000517:prevention & control*; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D007106:Immune Sera; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase