Treatment with edaravone attenuates ischemic brain injury and inhibits neurogenesis in the subventricular zone of adult rats after focal ischemia

Both good and bad from this, never heard of this before.
http://www.sciencedirect.com/science/article/pii/S0306452211012723

Abstract

Edaravone is a novel free radical scavenger that is clinically employed in patients with acute cerebral infarction. However, its effect on stroke-induced subventricular zone (SVZ) neurogenesis is largely unknown. In this study, we investigated the effect and underlying mechanism of edaravone administration on SVZ neurogenesis using a rat model of cerebral ischemia-reperfusion injury. Male Sprague–Dawley rats (200–250 g) were divided into sham operated (n=15), control (n=50), and edaravone-treated (n=50) groups. Rats in the control and edaravone-treated groups underwent 90 min of middle cerebral artery occlusion (MCAO) following reperfusion. Immediately and 12 h after MCAO, the rats received either normal saline (control group) or edaravone (edaravone-treated group) intraperitoneally. 5-bromo-2-deoxyuridine (BrdU) was used to label proliferating cells. Six, 12, and 24 hours after ischemia, reactive oxygen species (ROS) generation, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) protein levels in ischemic ipsilateral SVZ were determined. Immunohistochemistry staining for BrdU and doublecortin (DCX) was performed at 1, 4, and 7 days after ischemia. Treatment with edaravone not only mitigated cerebral infarct size (P<0.05) and neurological defects (P<0.05), but also decreased cell proliferation and neural progenitor cells in the ischemic ipsilateral SVZ (P<0.05). Additionally, edaravone reduced effectively ROS generation and HIF-1α as well as VEGF protein levels in the ischemic ipsilateral SVZ (P<0.05). These findings indicate that administration with edaravone, via repressing HIF-1α signaling pathway, inhibits SVZ neurogenesis in rats after cerebral ischemia-reperfusion injury.

Highlights

▶Edaravone, a novel free radical scavenger, is effective in reducing brain damage after stroke. ▶Edaravone decreased SVZ neurogenesis after stroke. ▶Repressing ROS and HIF-1α signaling may contribute to the inhibition of neurogenesis. ▶Our findings reveal the role of ROS and HIF-1 α signaling in neurogenesis after stroke.

Key words: neurogenesis; reactive oxygen species; hypoxia-inducible factor 1α; cerebral ischemia; reperfusion injury

Abbreviations: ANOVA, analysis of variance; BrdU, 5-bromo-2-deoxyuridine; DCX, doublecortin; EPO, erythropoietin; HIF-1α, hypoxia-inducible factor 1α; MCAO, middle cerebral artery occlusion; mNSS, modified neurological severity score; NSC, neural stem cell; NSCs, neural stem cells; NSPCs, neural stem/progenitor cells; RMS, rostral migratory stream; ROS, reactive oxygen species; SVZ, subventricular zone; TRITC, tetramethyl rhodamine isothiocyanate; VEGF, vascular endothelial growth factor

Article Outline

• Experimental procedures
• • Animal modeling
  • Immunohistochemistry
  • Western blotting
  • In situ superoxide detection
  • Cell counts
  • Statistical analysis
• Results
• • Edaravone decreased infarct size and neurological deficits
  • Edaravone reduced BrdU-labeled cells in the SVZ after ischemia
  • Edaravone decreased neural progenitor cells in the SVZ after ischemia
  • Edaravone repressed HIF-1α and VEGF protein expressions in the SVZ after injury
  • Edaravone decreased ROS generation in the SVZ after injury
• Discussion
• Conclusions
• Uncited reference
• Acknowledgments
• References
• 
  

So what is more important, decreased infarct size or better neurogenesis? Who is going to study this?