Brain and Behavior (Oct 2023)

Cottonseed oil alleviates ischemic stroke injury by inhibiting ferroptosis

  • Miao Sun,
  • Min Liu,
  • Qingxiao Li,
  • Xiaoying Zhang,
  • Siyuan Liu,
  • Huikai Yang,
  • Le Yang,
  • Jiahe Tian,
  • Weidong Mi,
  • Yulong Ma

DOI
https://doi.org/10.1002/brb3.3179
Journal volume & issue
Vol. 13, no. 10
pp. n/a – n/a

Abstract

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Abstract Introduction Ferroptosis has recently been recognized as a new cause of ischemia reperfusion injury due to blood–brain barrier (BBB) disruption followed by secondary iron‐loaded transferrin (TF) influx. As a novel and independent cell death pathway, ferroptosis was characterized by iron‐dependent lipid peroxidation, decline of GSH, GPX4, and shrinking mitochondria. Cottonseed oil (CSO), a liposoluble solvent, can alleviate ischemia stroke injuries and oxidative stress. However, the effect of CSO on ischemic stroke–induced ferroptosis has not been explored. In this study, we investigated the effect of CSO on ferroptosis caused by cerebral ischemic injury in rats. Methods We conducted the subcutaneous injection of 1.3 mL/kg CSO every other day for 3 weeks on rats with middle cerebral artery occlusion–reperfusion (MCAO‐R) injury. We used Garcia Test, TTC staining, HE, Nissl and NeuN staining, Evans blue test, 68Ga‐citrate PET, Western blot, immunofluorescence staining, Elisa kits, and transmission electron microscopy to detect the infarct volume, neural injuries, and ferroptosis‐related indexes. Results CSO treatment could significantly ameliorate MCAO‐R‐induced neurological dysfunction in a male rat model. Furthermore, it reduced infarct volume and neuronal injuries; protected BBB integrity; reduced the influx of iron ion, TF, and TF receptors; up‐regulated anti‐ferroptosis proteins (GPX4, xCT, HO1, FTH1), while down‐regulating ferroptosis‐related protein ACSL4; increased the activity of GSH and SOD; and decreased MDA and LPO levels. Mitochondrial destruction induced by ischemic stroke was also alleviated by CSO treatment. Conclusion CSO treatment can alleviate ischemic stroke injury via ferroptosis inhibition, which provides a new potential therapeutic mechanism for CSO neuroprotection against ischemic stroke.

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