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Journal of Neurosurgical Sciences 2002 June;46(2):55-9

Copyright © 2002 EDIZIONI MINERVA MEDICA

lingua: Inglese

The role of constitutive nitric oxide synthase in pathogenesis of secondary lesion after spinal cord injury. Preliminary results

Miscusi M.

Section of Neurosurgery, Department of Neurological Sciences and Vision, University of Verona, Verona


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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/mm2 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.

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