Commentary: Inhibition of gene expression—A novel strategy for cerebral protection during deep hypothermic circulatory arrest

Abstract

In their article in this edition of the Journal, Gao and coworkers 1 have demonstrated that inhibition of long noncoding RNA (lncRNA) growth arrest specific 5 (GAS5) expression attenuates cerebral injury in a rodent model of deep hypothermic circulatory arrest (DHCA). This protection, which was mediated through the microRNA-23a (miR-23a)/phosphatase and tensin homolog (PTEN) pathway, resulted in an increased expression of miR-23a, a decreased incidence of apoptosis in the hippocampus, and improved spatial learning and memory function. Gao and coworkers 1 have provided new insight into the mechanisms for cerebral injury during DHCA and how such injury may alter learning and memory function. Nevertheless, there are several limitations with this study.As noted by Gao and coworkers, 1 a rodent DHCA model may not replicate the cerebral changes seen in human patients undergoing DHCA. Furthermore, it is unclear whether the changes in neuronal cell apoptosis that were produced in their rodent model will produce similar, if any neurologic deficits in humans. Transfection of the adenovirus-associated vector of GAS5 required 14 days, and the vector was administered by way of intraventricular injection. Such a time-consuming technique would not be applicable for patients undergoing aortic surgery requiring DHCA on an urgent or emergency basis. Furthermore, the need for an intracerebral injection increases the risk of additional morbidity in an already high-risk group of patients. Finally, because GAS5 has been shown to inhibit cell proliferation and promote apoptosis in gliomas, 2 the inhibition of GAS5 in humans has the potential to increase their susceptibility to malignant cerebral tumors.Gao and coworkers 1 are to be congratulated on performing an elegant set of experiments in a rodent model to demonstrate the potential of lncRNA GAS5 inhibition as a novel mechanism for cerebral protection during DHCA. Further studies will be necessary in a large animal model to demonstrate its potential applicability to human patients undergoing procedures involving DHCA. References 1. Gao S, Gu T, Shi E, Tang R, Liu J, Shi J. Inhibition of long noncoding RNA growth arrest-specific 5 attenuates cerebral injury induced by deep hypothermic circulatory arrest in rats. J Thorac Cardiovasc Surg. 2020;159:50-9. 2. Zhao X, Wang P, Liu J, Zheng J, Liu Y, Chen J, et al. GAS5 exerts tumorsuppressive function in human glioma cells by targeting miR-222. Mol Ther. 2015;23:1899-911.