Abstract
Remote ischemic preconditioning (RiPC) is the process where preconditioning ischemia protects the organs against the subsequent index ischemia. RiPC is a protective method for brain damage. This study is to explore the effect and mechanism of RiPC in cerebral ischemia injury in rats through regulation of miR-204-5p/BRD4 expression. Middle cerebral artery occlusion (MCAO) rat model and glucose deprivation (OGD) neuron model were established. The effect of RiPC on neurological deficits, cerebral infarct size, autophagy marker, inflammatory cytokines and apoptosis was evaluated. miR-204-5p expression was analyzed using RT-qPCR, and then downregulated using miR-204-5p antagomir to estimate its effect on MCAO rats. The downstream mechanism of miR-204-5p was explored. RiPC promoted autophagy, reduced cerebral infarct volume and neurological deficit score, and alleviated apoptosis and cerebral ischemia injury in rats, with no significant effects on healthy rat brains. RiPC up-regulated miR-204-5p expression in MCAO rats. miR-204-5p knockdown partially reversed the effect of RiPC. RiPC promoted autophagy in OGD cells, and attenuated inflammation and apoptosis. miR-204-5p targeted BRD4, which partially reversed the effect of miR-204-5p on OGD cells. RiPC activated the PINK1/Parkin pathway via the miR-204-5p/BRD4 axis. In conclusion, RiPC activated the PINK1/Parkin pathway and prevented cerebral ischemia injury by up-regulating miR-204-5p and inhibiting BRD4.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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The authors acknowledge operating grant support from the National Natural Science Foundation of China (grants no: 82071331, 81870942, and 81520108011), National Key Research and Development Program of China (grant no: 2018YFC1312200), Innovation Scientists and Technicians Troop Constructions Projects of Henan Province of China (for MX) and Jonit Project of Henan Province Medical Science and Techenology Research Plan (grant no: LHGJ20190313).
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YMJ contributed to the study concepts, study design, and definition of intellectual content; YMJ, JLW contributed to the literature research; YMJ contributed to the manuscript preparation and MZX contributed to the manuscript editing and review; YMJ, MZX, JLW, YJJ contributed to the experimental studies and data acquisition; YMJ, MZX, JLW, YJJ contributed to the data analysis and statistical analysis. All authors read and approved the final manuscript.
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Jiao, Y., Wang, J., Jia, Y. et al. Remote ischemic preconditioning protects against cerebral ischemia injury in rats by upregulating miR-204-5p and activating the PINK1/Parkin signaling pathway. Metab Brain Dis 37, 945–959 (2022). https://doi.org/10.1007/s11011-022-00910-z
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DOI: https://doi.org/10.1007/s11011-022-00910-z