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

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


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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