Improved functional outcome after spinal cord injury in iNOS-deficient mice

Abstract

Study design: Functional outcome was evaluated following experimental compression-type spinal cord injury (SCI) in wild-type mice and knockout mice, lacking the inducible nitric oxide synthase (iNOS) gene. Objectives: To evaluate the role of the nitric oxide generating enzyme iNOS in SCI. Methods: The experimental animals were subjected to an extradural compression of the thoracic spinal cord. Functional outcome was studied during the first 2 weeks post-injury using a scoring system for assessment of hind limb motor function. Results: Injury resulted in initial paraplegia followed by gradual improvement of motor function in most cases. Mice lacking the iNOS gene (iNOSÀ/À) clearly tended to have a better functional outcome than wild-type mice. The difference was significant on day 14 after injury. Conclusion: In accordance with a few earlier experimental studies, showing beneficial effects of pharmacological iNOS inhibition, the present report would indicate a destructive influence of iNOS following spinal cord trauma.

Inhibition of the Ca2+-Dependent K+Channel,KCNN4/KCa3.1, Improves Tissue Protection and Locomotor Recovery after Spinal Cord Injury

“…IL-1␤ contributes to glutamate-mediated damage following SCI, and blocking IL-1␤ improves locomotor recovery (Liu et al, 2008). Finally, reducing iNOS expression has been associated with neuroprotection and better functional outcomes after SCI (Isaksson et al, 2005;Ló pez-Vales et al, 2006). iNOS is not expressed in the healthy adult CNS, but after spinal cord injury, proinflammatory cytokines can induce it in microglia and astrocytes (Murphy, 2000;Xu et al, 2001;Rathore et al, 2008), and its expression is seen as late as 14 d after injury.…”

IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis

“…Increased expression of iNOS mRNA is also found in EAE, and inhibition of iNOS protects animals from EAE (17). The destructive influence of iNOS following spinal cord trauma has been demonstrated in iNOS KO mice, which had better functional outcomes from compression injury than wild-type controls (18).…”

Significant correlation between cerebrospinal fluid nitric oxide concentrations and neurologic prognosis in incomplete cervical cord injury

“…Excessive NO production derived from iNOS has cytotoxic effects [5] and induces neuronal apoptosis, causing neural degeneration and neurodysfunction [1,9]. Compared to wild-type mice, iNOS-gene deficient mice have a significantly better functional outcome after SCI [15]. Administration of a NOS blocker reduces neurologic deterioration [3].…”