ATN-161 Ameliorates Ischemia/Reperfusion-induced Oxidative Stress, Fibro-inflammation, Mitochondrial damage, and Apoptosis-mediated Tight Junction Disruption in bEnd.3 Cells

We have previously demonstrated the significance of endothelial cell-expressed α5β1 integrin in ischemic stroke, having shown that α5β1 integrin endothelial cell-selective knockout mice are significantly resistance to ischemic stroke injury via preservation of the tight junction protein claudin-5 and subsequent stabilization of the blood–brain barrier

Narayanappa Amruta; Gregory Bix


Scholarcy highlights

  • Ischemic stroke, a disruption of blood flow to a part of the brain most commonly due to a blood clot accounts for ~ 80% of all strokes and is a significant cause of morbidity and mortality
  • Western blot analysis showed that oxygen and glucose deprivation and reperfusion induces NLRP3 inflammasome expression levels in bEND.3 cells challenged with 6 h oxygen–glucose deprivation and 24 h of reoxygenation compared with control cells)
  • Immunofluorescence of NLRP3 in bEND.3 cells shows highly induced NLRP3 expression in OGD/R challenged cells compared to cells with vehicle or ATN-161 treatment)
  • Fluorescence images of intracellular reactive oxygen species, as measured by DCFH2DA dye, showed highly induced intracellular ROS production in OGD/R challenged cells compared to cells with vehicle or ATN-161 treatment)
  • Our study identified that OGD/R induced inflammation, oxidative stress, apoptosis, mitochondrial depolarization, and fibrosis mediated tight junction integrity, potentially via induction of integrin α5, NLRP3, p-FAK, and p-AKT signaling in mouse brain endothelial cells
  • ATN-161 was safe and well-tolerated in several phase I and phase II clinical oncology studies, supporting its potential as a “shovel-ready” clinical stroke therapeutic

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