Affiliation:
1. Southern Medical University
2. Southeast University Zhongda Hospital
3. Nanjing Jinling Hospital: East Region Military Command General Hospital
4. Nanjing BenQ Medical Center
Abstract
Abstract
Therapeutic hypothermia (HT) is an important treatment after cardiac arrest to mitigate cerebral ischemia-reperfusion (I/R) injury, but the underlying mechanism is not clear. Studies have shown that cold-inducible RNA binding protein (CIRP), as a stress-response protein, exerts key role on improvement of neurological outcome after therapeutic hypothermia treatment in the global ischemia. Thus, this study focused on investigating the role of CIRP in hippocampal neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and exploring relative mechanisms. In our study, the results of biochemical detection, flow cytometry and western blot showed that HT could significantly inhibit OGD/R-induced neuronal apoptosis and oxidative stress. The results of RT-PCR and western blot indicated that HT could induce CIRP over-expression in neurons and reverse the down-regulation of CIRP induced by OGD/R. In addition, over-expression of CIRP could reduce the release of ROS induced by OGD/R through reducing MDA levels and increasing the level of SOD and GSH, and alleviated OGD/R-induced neuronal apoptosis by down-regulating Caspase-3 expression and up-regulating Bcl-2 expression. Furthermore, CIRP silencing enhanced neuronal OGD/R-induced apoptosis and oxidative stress. Meanwhile, neuron ultrastructure was visualized by transmission electron microscope (TEM). As expected, neurons were seriously damaged and mitochondrial membrane ruptured after OGD/R injury, which were attenuated by CIRP over-expression or HT. Taken together, our results showed that CIRP resisted OGD/R-induced neuronal injury by exhibiting anti-apoptotic and anti-oxidative properties. To sum up, targeting CIRP offers potential therapeutic implications in the treatment of brain I/R injury.
Publisher
Research Square Platform LLC
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