Intracerebral hemorrhage (ICH) is one type of stroke with a high incidence and mortality. Mitochondria provide energy for various life processes and regulate calcium-mediated signaling pathways by taking up calcium ions from cytoplasm. Mitochondrial calcium uptake family 3 (MICU3) is a tissue-specific enhancer of mitochondrial calcium uptake. The effects and mechanisms of MICU3 in ICH are unknown. In this study, we aimed to explore the role of MICU3 in ICH in rats and neuronal models. First, we constructed ICH model both in vivo and in vitro and observed increased expression of MICU3. Then lentivirus was transduced to knock down MICU3. We observed that knockdown of MICU3 significantly reduced mitochondrial uptake of calcium in primary neurons. Moreover, the downregulation of MICU3 attenuated cell apoptosis and decreased the accumulation of reactive oxygen species (ROS). Recovery of neurobehavioral and cognitive function also benefited from downregulation of MICU3. The findings demonstrated that MICU3 played an important role in cell apoptosis, oxidative stress, and maintenance of mitochondrial structure and function, and promoted rehabilitation of neurobehavior. In conclusion, MICU3 is expected to be a molecular marker and a potential therapeutic target for ICH.
Keywords: Cell necrosis and apoptosis; Intracerebral hemorrhage; Mitochondria; Mitochondrial calcium uptake family 3; Secondary brain injury.
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