SCO-spondin-derived peptide NX210 rescues neurons from cerebral ischemia/reperfusion injury through modulating the Integrin-β1 mediated PI3K/Akt pathway

 So human testing needed. Will never occur since we have NO leadership and NO strategy anywhere in stroke. You, your children and grandchildren are screwed until we get survivors in charge.

SCO-spondin-derived peptide NX210 rescues neurons from cerebral ischemia/reperfusion injury through modulating the Integrin-β1 mediated PI3K/Akt pathway

Author links open overlay panelLiyuYang^acJinZhu^acLiYang^bcYunhaoGan^acDiHu^acJingZhao^bc

YongZhao^ac

https://doi.org/10.1016/j.intimp.2022.109079Get rights and content

Highlights

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NX210 increased viability and reduced cytotoxicity after OGD/R injury in primary cortical neurons.

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NX210 reduced the infarct volume and decreased brain edema after MCAO/R injury in rats.

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NX210 neuroprotective effects were exerted via an integrin-β1 Integrin-β1/PI3K/Akt pathway.

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NX210 is a potential therapeutic agent against cerebral ischemia/reperfusion injury.

Abstract

Ischemic stroke is a common condition with high morbidity and mortality, causing irreversible neuronal damage and seriously affecting neurological function. There has been no ideal effective treatment so far. The NX210 peptide is derived from the thrombospondin type 1 repeat (TSR) sequence of SCO-spondin, and has been reported to exert various neurogenic properties. This study investigated whether NX210 had therapeutic effects and possible underlying mechanisms against cerebral ischemia/reperfusion (I/R). Therefore, primary embryonic rat cortical neurons and Sprague–Dawley (SD) rats that were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively, were treated with or without NX210. We found that NX210 reduced OGD/R-induced cell viability loss and cytotoxicity. NX210 decreased cerebral infarct volume and brain edema, ameliorated neurological dysfunction, attenuated oxidative stress damage, and diminished neuronal apoptosis in MCAO/R rats. Furthermore, western blot analysis shown that treatment with NX210 up-regulated the expression of Integrin-β1, phosphorylated-PI3K (p-PI3K) and phosphorylated-Akt (p-Akt). The Integrin-β1 specific inhibitor, ATN-161, was used to identify pathways involved. The anti-oxidation activities and anti-apoptosis of NX210 was reversed by treatment with ATN-161. Overall, our results indicated that NX210 prevents oxidative stress and neuronal apoptosis in cerebral I/R via upregulation of the Integrin-β1/PI3K/Akt signaling pathway. These results indicated that NX210 may be a promising therapeutic candidate for ischemic stroke.