The role of constitutive nitric oxide synthase in pathogenesis of secondary lesion after spinal cord injury. Preliminary results.
BACKGROUND
Secondary lesion (SL) is an early phenomenon of cellular death following spinal cord injury (SCI). Nitric oxide (NO) could be involved in its pathogenesis. NO is a gaseous metabolite produced by 2 constitutive isoforms of NO synthase (cNOS), constantly active, and by 1 inducible isoform (iNOS), synthesized during inflammation and able to produce large amount of NO. High concentrated NO is toxic for cells; therefore, NO concentration is strictly and finely regulated. We suppose that major inhibitory effect on the iNOS expression is represented by the same physiological concentration of NO, synthesized by cNOS. The aim of this study is to assess the role of the 2 cNOS in pathogenesis of SL after SCI in rat.


METHODS
A dorsal SCI has been performed on rats (n=5) by a vascular clip (50 g/mm(2) for 15"). Fifteen minutes after trauma, activity of nNOS and eNOS has been measured (U/mg) in the cervical, dorsal and lumbar segments of spinal cord. Uninjured rats (n=5) served as control group. m-RNA for iNOS in untreated rats (n=2) has been also investigated by Northern blotting.


RESULTS
In injured rats nNOS activity has shown a reduction in dorsal and lumbar segments, compared to the control group. eNOS activity, highly variable in the control group, has not been detectable in injured spinal cord. i-NOS mRNA has not been found in spinal cord of uninjured rats.


CONCLUSIONS
These results would be in line with our hypothesis and provide the bases for other investigations. New therapeutic strategies for SL prevention, based on the modulation of cNOS, will be evaluated.
Miscusi
M
M
Section of Neurosurgery, Department of Neurological Sciences and Vision, University of Verona, Verona, Italy. m.miscusi@libero.it
D000818:Animals; D015152:Blotting, Northern; D015971:Gene Expression Regulation, Enzymologic; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013117:Spinal Cord Compression / Q000201:enzymology* / Q000235:genetics; D013904:Thoracic Vertebrae / Q000201:enzymology / Q000293:injuries
D012313:RNA; D019001:Nitric Oxide Synthase