Acute Molecular Perturbation of Inducible Nitric Oxide Synthase with an Antisense Approach Enhances Neuronal Preservation and Functional Recovery after Contusive Spinal Cord Injury

Object. The inflammatory cells that accumulate at the damaged site after spinal cord injury (SCI) may secrete interleukin-6 (IL-6), a mediator known to induce the expression of inducible nitric oxide synthase (iNOS). Any increased production of NO by iNOS activity would aggravate the primary neurological damage in SCI. If this mechanism does occur, the direct or indirect effects of IL-6 antagonists on iNOS activity should modulate this secondary injury. In this study, the authors produced spinal cord damage in rats and applied anti—rat IL-6 antibody to neutralize IL-6 bioactivity and to reduce iNOS. They determined the spinal cord tissue activities of Na+-K+/Mg++ adenosine-5′-triphosphatase (ATPase) and superoxide dismutase, evaluated iNOS immunoreactivity, and examined ultrastructural findings to assess the results of this treatment. Methods. Seventy rats were randomly allocated to four groups. Group I (10 rats) were killed to provide normal spinal cord tissue for testing. In Group II 20 rats underwent six-level laminectomy for the effects of total laminectomy alone to be determined. In Group III 20 rats underwent six-level T2–7 laminectomy and SCI was produced by extradural compression of the exposed cord. The same procedures were performed in the 20 Group IV rats, but these rats also received one (2 µg) intraperitoneal injection of anti—rat IL-6 antibody immediately after the injury and a second dose 24 hours posttrauma. Half of the rats from each of Groups II through IV were killed at 2 hours and the other half at 48 hours posttrauma. The exposed cord segments were immediately removed and processed for analysis. Conclusions. The results showed that neutralizing IL-6 bioactivity with anti—rat IL-6 antibody significantly attenuates iNOS activity and reduces secondary structural changes in damaged rat spinal cord tissue.

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Allicin protects spinal cord neurons from glutamate-induced oxidative stress through regulating the heat shock protein 70/inducible nitric oxide synthase pathway

Food & Function ◽

10.1039/c4fo00761a ◽

2015 ◽

Vol 6 (1) ◽

pp. 320-329 ◽

Cited By ~ 22

Author(s):

Shu-Guang Liu ◽

Peng-Yu Ren ◽

Guo-Yu Wang ◽

Shu-Xin Yao ◽

Xi-Jing He

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Heat Shock Protein 70 ◽

Underlying Mechanism ◽

Spinal Cord Neurons ◽

Cord Injury ◽

Oxide Synthase ◽

Inducible Nitric Oxide

We demonstrate that allicin may be used as an effective treatment for spinal cord injury, and that the potential underlying mechanism involves HSP70/iNOS pathway-mediated inhibition of oxidative stress.

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Epidural Cooling Minimizes Spinal Cord Injury after Aortic Cross-clamping through Induction of Nitric Oxide Synthase

Anesthesiology ◽

10.1097/aln.0b013e3181b764f6 ◽

2009 ◽

Vol 111 (4) ◽

pp. 818-825 ◽

Cited By ~ 8

Author(s):

Akiko Ishikawa ◽

Atsuo Mori ◽

Nobuyuki Kabei ◽

Akihiro Yoshitake ◽

Takeshi Suzuki ◽

...

Keyword(s):

Nitric Oxide ◽

Spinal Cord ◽

Blood Flow ◽

Nitric Oxide Synthase ◽

Cord Blood ◽

Inducible Nitric Oxide Synthase ◽

Spinal Cord Blood Flow ◽

Cord Injury ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Background By using a U-shaped lumen catheter, the authors examined the effects of epidural cooling on spinal cord injury after aortic cross-clamping (ACC), with a focus on changes of spinal cord blood flow and expression of inducible nitric oxide synthase. Methods Sixteen pigs were randomized into two groups: Control group (n = 8) or Cooling group (n = 8). In the latter, epidural cooling started at 30 min (baseline) before 45 min of ACC and persisted for the next 30 min of reperfusion period. Spinal cord blood flow and somatosensory-evoked potentials were assessed during peri-ACC period. At 48 h, we evaluated hind limb function by using Tarlov score and expression of inducible nitric oxide synthase on spinal cord using immunohistochemistry. Results After ACC, spinal cord blood flow dropped to a similar extent in both groups. During the reperfusion period, spinal cord blood flow increased up to 113% (103-124%), median (interquartile range), level transiently and decreased to 32% (22-47%) level versus baseline in the Control group, whereas it increased and remained at 92% (86-97%) level in the Cooling group. Simultaneously, somatosensory-evoked potentials showed that onset of loss time was delayed and recovery time was shortened in the Cooling group. Tarlov scores in the Cooling group were significantly higher and accompanied by normal-appearing motor neurons and significantly greater expression of inducible nitric oxide synthase on spinal cord versus the Control group. Conclusions This study shows that epidural cooling during ACC minimized the risk of spinal cord injury, possibly by preventing delayed hypoperfusion and upregulating inducible nitric oxide synthase expression.

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