ADAM8 Activates NLRP3 Inflammasome to Promote Cerebral Ischemia-Reperfusion Injury.

Hongwei Lu, Yaqin Meng, Xinrui Han, Wei Zhang

Journal of healthcare engineering 2021

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Stroke is the leading cause of death and disability in humans. Strokes are classified as either ischemic or hemorrhagic. Ischemic stroke accounts for 70-80% of the cases. Inflammation is a key factor in ischemic brain injury. Studies have shown that inflammatory response induced by NLRP3 inflammasome is one of the root causes of brain damage in mice with cerebral ischemia. However, its specific mechanism in cerebral ischemia is still unclear. ADAM8 (a disintegrin and metalloproteases 8) is a transmembrane protein with different functions. It plays an important role in tumors and neuroinflammation-related diseases. However, the role and molecular mechanism of ADAM8 in cerebral ischemia injury are still unclear. This study aims to evaluate the role of ADAM8 in cerebral ischemic injury and explore its signal transduction mechanism. This experiment shows that ADAM8 can significantly cause neurological deficits in MCAO mice and can substantially cause ipsilateral cerebral edema and cerebral infarction in MCAO mice. In addition, ADAM8 can significantly induce cortical cell apoptosis in MCAO mice, leading to the loss of neurons and the expression of proinflammatory factors COX2, iNOS, TNFα, and IL-6. Importantly, we confirmed that ADAM8 mediates the inflammatory response by promoting the activation of NLRP3 inflammasome, microglia, and astrocytes. These results indicate that ADAM8 may be a candidate drug target for the prevention and treatment of the cerebral ischemic injury. Copyright © 2021 Hongwei Lu et al.

Citation

Hongwei Lu, Yaqin Meng, Xinrui Han, Wei Zhang. ADAM8 Activates NLRP3 Inflammasome to Promote Cerebral Ischemia-Reperfusion Injury. Journal of healthcare engineering. 2021;2021:3097432