期刊
ANTIOXIDANTS
卷 11, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/antiox11071257
关键词
blood-brain barrier; ischemic stroke; mitochondrial ferritin; iron; endothelial cells
资金
- National Natural Science Foundation of China [31520103908]
- Key Project of Natural Science Foundation of Hebei Province, China [E2021205003]
Blood-brain barrier (BBB) breakdown is a common feature of ischemic stroke. This study reveals that overexpression of mitochondrial ferritin (FtMt) can attenuate BBB disruption in an ischemia-reperfusion (I/R) injury model by inhibiting iron dysregulation and reactive oxygen species accumulation. These findings provide novel insights into the protective role of FtMt in maintaining BBB integrity during ischemic stroke.
Blood-brain barrier (BBB) breakdown, a characteristic feature of ischemic stroke, contributes to poor patient outcomes. Brain microvascular endothelial cells (BMVECs) are a key component of the BBB and dysfunction or death of these cells following cerebral ischemia reperfusion (I/R) injury can disrupt the BBB, leading to leukocyte infiltration, brain edema and intracerebral hemorrhage. We previously demonstrated that mitochondrial ferritin (FtMt) can alleviate I/R-induced neuronal ferroptosis by inhibiting inflammation-regulated iron deposition. However, whether FtMt is involved in BBB disruption during cerebral I/R is still unknown. In the present study, we found that FtMt expression in BMVECs is upregulated after I/R and overexpression of FtMt attenuates I/R-induced BBB disruption. Mechanistically, we found that FtMt prevents tight junction loss and apoptosis by inhibiting iron dysregulation and reactive oxygen species (ROS) accumulation in I/R-treated BMVECs. Chelating excess iron with deferoxamine alleviates apoptosis in the brain endothelial cell line bEnd.3 under oxygen glucose deprivation followed by reoxygenation (OGD/R) insult. In summary, our data identify a previously unexplored effect for FtMt in the BBB and provide evidence that iron-mediated oxidative stress in BMVECs is an early cause of BMVECs damage and BBB breakdown in ischemic stroke.
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