**4. miRNAs in ischemic conditions**

Not only coding mRNA but also various types of ncRNA, which have significant regulatory potential, are involved in the response to ischemia. Much current attention worldwide is paid to the study of the features of the functioning of mRNA, miRNA, and long ncRNA as regulators in the mechanisms of pathogenesis and neuroprotection in ischemic conditions [30–35].

miRNAs are ncRNA molecules with a length of 20–22 nt. They act by direct interaction with target sites on mRNA, which leads to the degradation of mRNA or repression of its translation [36, 37]. miRNAs are critical regulators of central nervous system plasticity and play an important role in ischemia. In particular, miRNA is actively involved in the response to ischemic brain damage [38, 39]. Following ischemic brain damage, miRNAs can play the role of both neuroprotective agents and contribute to pathological manifestations. mRNA of the AMPA receptor subunit GluA2/GluR2 (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor) is the target of miR-181a. Thus, an increase in miR-181a expression may be neuroprotective. Indeed, there are many examples of where miRNAs contribute to the development of the pathological process following ischemic brain damage. Thus, miR-132 increases the expression of the NMDA receptor, which selectively binds N-methyl-d-aspartate, increasing the risk of excitotoxicity [40, 41]. Therefore, the use of miR-132 antagonists may have a neuroprotective effect. Herzog et al. studied the role of steroid hormones 17β-estradiol (E2) and progesterone (P) in the brain as regulatory factors for miR-223-3p, miR-200c-3p, miR-375-3p, miR-199-3p, miR-214-3p, and their target genes in the tMCAO model [42]. The levels of these miRNAs are increased at 12 and 72 h after tMCAO. E2 or P selectively dampened miR-223 and miR-214 but further boosted miR-375 levels. The expression of the genes for NR2B and GRIA2, which are targets for miR-223, was reduced after tMCAO, and E2 and P canceled this effect. Steroid therapy inhibited tMCAO-induced increases in the expression of genes for BCL-2 and RAD1, which are targets for miR-375. Thus, E2 and P have a role as indirect regulators of translation of proapoptotic and pro-inflammatory genes, which leads to the weakening of ischemic damage of tissue [42].
