Thrombopoietin could protect cerebral tissue against ischemia-reperfusion injury by suppressing NF-κB and MMP-9 expression in rats

Int J Med Sci. 2018 Aug 10;15(12):1341-1348. doi: 10.7150/ijms.27543. eCollection 2018.

Abstract

Objective: To determine the neuroprotective effects and underpinning mechanisms of thrombopoietin (TPO), Matrix Metalloproteinase-9(MMP-9) and Nuclear Factor-κB (NF-κB) after focal cerebral ischemia-reperfusion in rats. Methods: Male rats underwent 2 hours of right middle cerebral artery occlusion (MCAO) followed by 22 hours of reperfusion. PBS or TPO (0.1ug/kg) was administered from caudal vein before reperfusion. Neurologic deficits, brain edema, Evans blue (EB) extravasation, NF-κB and MMP-9 expression were subsequently examined. Results: Ischemia-reperfusion injury produced a large area of edema. TPO significantly reduced edema and alleviated neurologic deficits after ischemia-reperfusion. Ischemia-induced increases of NF-κB, MMP-9 and Evans blue extravasation were reduced by TPO intervention. Conclusion: TPO improved neurological function and ameliorated brain edema after stroke, partly by reducing the ischemia-induced increase of NF-κB and MMP-9.

Keywords: Ischemia-Reperfusion (IR); Matrix Metalloproteinase-9 (MMP-9); Nuclear factor-κB (NF-κB); Thrombopoietin (TPO).

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Brain Edema* / complications
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / etiology
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / metabolism*
  • Neuroprotective Agents
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury*
  • Stroke / complications
  • Thrombopoietin / pharmacology*

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • Thrombopoietin
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat