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Updated: Aug 11, 2026
A Neurosphere Assay to Evaluate Endogenous Neural Stem Cell Activation in a Mouse Model of Minimal Spinal Cord Injury
Published on: September 13, 2018
Modulation of nitric oxide homeostasis in a mouse model of spinal cord injury
Tiziana Genovese1, Emanuela Mazzon, Sofia Mariotto
1Institute of Pharmacology, University of Messina, Italy.
Object:
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.
Insights
Inhibition of inducible nitric oxide synthase (iNOS) reduces secondary damage after spinal cord injury (SCI). This finding suggests iNOS plays a key role in SCI pathogenesis and offers a potential therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Traumatic spinal cord injury (SCI) causes primary damage followed by secondary damage, including progressive cell death.
- Inducible nitric oxide synthase (iNOS) is implicated in the inflammatory cascade following SCI.
Purpose of the Study:
- To investigate the role of iNOS in an experimental mouse model of SCI.
- To determine if inhibiting iNOS can mitigate secondary damage after SCI.
Main Methods:
- Wild-type (iNOS+/+) mice were subjected to SCI.
- Inflammatory markers such as nitrotyrosine formation, PARP activation, and neutrophil infiltration were assessed.
- Histopathological changes in spinal cord tissue were evaluated.
Main Results:
- SCI in wild-type mice rapidly induced an inflammatory response, indicating iNOS involvement.
- Genetic inhibition of iNOS significantly reduced secondary damage post-SCI.
- Inhibition of iNOS prevented the SCI-induced decrease in neuronal and endothelial NOS activity.
Conclusions:
- iNOS plays a critical role in the secondary damage cascade following SCI.
- Genetic inhibition of iNOS demonstrates therapeutic potential for reducing SCI-induced tissue damage.
- Targeting iNOS may offer a novel strategy for managing spinal cord injuries.
