Modulation of nitric oxide homeostasis in a mouse model of spinal cord injury.
OBJECTIVE
A traumatic spinal cord injury (SCI) immediately induces primary damage, and this is followed by secondary damage characterized by a series of events among which is a progressive extension of cell death within the damaged tissue. In this study, the authors investigated the role of inducible nitric oxide synthase (iNOS) in an experimental model of SCI in mice.


METHODS
In wild-type (iNOS+/+) mice, SCI rapidly induced an inflammatory response as shown by nitrotyrosine formation, activation of the nuclear enzyme poly(adenosine diphosphate-ribose) polymerase (PARP), neutrophil infiltration, and spinal cord tissue histopathological changes, indicating the involvement of iNOS-derived massive amounts of NO in SCI.


CONCLUSIONS
Genetic inhibition of iNOS, however, resulted in a significant reduction in secondary damage, and this therapeutic efficacy was associated with the prevention of an SCI-induced drop in neuronal and endothelial NOS activity.
Genovese
Tiziana
T
Institute of Pharmacology, University of Messina, Italy.
Mazzon
Emanuela
E
Mariotto
Sofia
S
Menegazzi
Marta
M
Cardali
Salvatore
S
Conti
Alfredo
A
Suzuki
Hisanori
H
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
D000818:Animals; D016923:Cell Death; D004195:Disease Models, Animal; D006706:Homeostasis; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II