Inhibition of NOX2 reduces locomotor impairment, inflammation, and oxidative stress after spinal cord injury

Journal of Neuroinflammation

Kimberly R. Byrnes¹  Sara Bermudez¹  Guzal Khayrullina¹ 

[1] Anatomy, Physiology and Genetics Department, Uniformed Services University, Room B2048, 4301 Jones Bridge Road, Bethesda 20814, MD, USA

关键词: Oxidative stress;    Spinal cord injury;    Inflammation;    Microglia;    Polarization;    NOX2;   

Others  :  1227053
DOI  :  10.1186/s12974-015-0391-8

 received in 2015-06-04, accepted in 2015-09-03,  发布年份 2015

【 摘 要 】

Background

Spinal cord injury (SCI) results in the activation of the NADPH oxidase (NOX) enzyme, inducing production of reactive oxygen species (ROS). We hypothesized that the NOX2 isoform plays an integral role in post-SCI inflammation and functional deficits.

Methods

Moderate spinal cord contusion injury was performed in adult male mice, and flow cytometry, western blot, and immunohistochemistry were used to assess NOX2 activity and expression, inflammation, and M1/M2 microglia/macrophage polarization from 1 to 28 days after injury. The NOX2-specific inhibitor, gp91ds-tat, was injected into the intrathecal space immediately after impact. The Basso Mouse Scale (BMS) was used to assess locomotor function at 24 h post-injury and weekly thereafter.

Results

Our findings show that gp91ds-tat treatment significantly improved functional recovery through 28 days post-injury and reduced inflammatory cell concentrations in the injured spinal cord at 24 h and 7 days post-injury. In addition, a number of oxidative stress markers were reduced in expression at 24 h after gp91ds-tat treatment, which was accompanied by a reduction in M1 polarization marker expression.

Conclusion

Based on our findings, we now conclude that inhibition of NOX2 significantly improves outcome after SCI, most likely via acute reductions in oxidative stress and inflammation. NOX2 inhibition may therefore have true potential as a therapy after SCI.

【 授权许可】

   
2015 Khayrullina et al.

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