**8. Conclusion**

The data presented in this review indicate that in addition to protein-coding mRNA, ncRNAs play an important role in the regulation of intracellular processes, both under normal conditions and in pathologies. An active study of the features of the functioning of ncRNAs in ischemia is of exceptional importance for the development of new strategies for neuroprotection and repair of nerve tissue and for the development of effective new drugs. circRNAs are a new class of RNAs that have enhanced resistance and preferential brain-specific expression. An analysis of circRNA-miRNA-mRNA interactions is an important component of any detailed study of the mechanisms of damage and regeneration in the case of pathological effects and the action of therapeutic agents, especially during the therapeutic window, when treatment is possible and most effective.

#### **Acknowledgements**

This study was funded by the Russian Science Foundation (grant number 19-14-00268).

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**Author details**

Russian Federation

Ivan B. Filippenkov\*, Lyudmila V. Dergunova and Svetlana A. Limborska Institute of Molecular Genetics, Russian Academy of Sciences, Moscow,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: filippenkov@img.ras.ru

provided the original work is properly cited.

*The Role of Noncoding RNAs in Brain Cells during Rat Cerebral Ischemia*

*DOI: http://dx.doi.org/10.5772/intechopen.88402*

## **Conflict of interest**

The authors declare no conflict of interest.

*The Role of Noncoding RNAs in Brain Cells during Rat Cerebral Ischemia DOI: http://dx.doi.org/10.5772/intechopen.88402*

*Non-Coding RNAs*

ischemia.

**8. Conclusion**

**Acknowledgements**

**Conflict of interest**

19-14-00268).

the neurotransmission genetic response.

homologous to the corresponding genes in rats. A sufficiently large number of binding sites are located inside the exons, which are also part of conservative circRNA. A functional role of circRNAs of the genes under study is implicated by ceRNA in the response of brain cells to ischemia. In an experimental ischemia-reperfusion model, we found numerous circRNAs that were differentially represented in the damage zone 24 h after occlusion. These circRNAs may be key modes for the regulation of

In a recent study, new important information was provided on the functioning of circRNA under ischemia conditions. Bai et al. showed that circRNA of DLGAP4 (circDLGAP4) functions as a miRNA sponge to diminish the activity of miR-143, which inhibits the expression of homologues of E6-AP C-terminal domain E3 ubiquitin ligase 1 [88]. The level of circDLGAP4 was significantly reduced in the plasma of patients with acute ischemic stroke and after tMCAO in mice. Upregulation of circDLGAP4 expression significantly reduced neurological deficit and reduced areas of infarction and damage to the blood-brain barrier in a mouse model of ischemia. Han et al. convincingly showed that circHECTD1 increases expression in the brain of mice after tMCAO, in human glioblastoma A172 cells under conditions of OGD/R, and in the blood of patients with acute ischemic stroke [89]. circHectd1 is involved in the regulation of the regenerative mechanisms of brain cells during ischemia. In particular, suppression of the expression circHectd1 was associated with a reduced infarction size in a mouse model of ischemia [89]. By interacting with MIR142, which negatively affects the mRNA level of the gene for 2,3,7,8-tetrachlorodibenzo-p-dioxin inducible poly [ADP-ribose] polymerase (TIPARP), circHECTD1 diminished the miRNA activity, with consequent circHECTD1-MIR142-TIPARP competition leading to the modulation of astrocyte activity through autophagy during cerebral

The data presented in this review indicate that in addition to protein-coding mRNA, ncRNAs play an important role in the regulation of intracellular processes, both under normal conditions and in pathologies. An active study of the features of the functioning of ncRNAs in ischemia is of exceptional importance for the development of new strategies for neuroprotection and repair of nerve tissue and for the development of effective new drugs. circRNAs are a new class of RNAs that have enhanced resistance and preferential brain-specific expression. An analysis of circRNA-miRNA-mRNA interactions is an important component of any detailed study of the mechanisms of damage and regeneration in the case of pathological effects and the action of therapeutic agents, especially during the therapeutic

This study was funded by the Russian Science Foundation (grant number

window, when treatment is possible and most effective.

The authors declare no conflict of interest.

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