## 3 Discussion
In this case, the expression and content of TNF\(\alpha\) in the cortical astrocytes was suppressed, which was expressed in the inhibition of necrosis and apoptosis caused by ischemia/reoxygenation. Along with the suppression of apoptosis and inflammation, SeNrs led to the activation of reactive astrogliosis, which was detected by increased expression of genes encoding protein markers of this process. It is known that reactive astrogliosis is a reaction of astrocytes to pathological conditions including trauma, brain aging, ischemia, bacterial or virus infections, and various neurodegenerative diseases [64; 65]. For a long time, it was believed that reactive astrogliosis has an extremely detrimental effect on the nervous system in the form of scar formation, which prevented the restoration of neurotransmission and brain functions after damage [65]. It is known that the reactivation of astrocytes is a complex stepwise process leading to both negative and positive effects on the brain, depending on the severity of the injury. In reactive astrogliosis, various changes occur in the patterns of gene expression of proteins responsible for the induction of cell proliferation and hypertrophy, which only in severe cases lead to the formation of scars. Moreover, there is strong evidence for the beneficial effects of scar formation as it can limit brain tissue damage and inflammation [64; 66; 67]. It is customary to subdivide reactive astrocytes into A1 and A2 types. Reactive A1 astrocytes are known to have lost many of the characteristic functions of astrocytes, including promoting neuron survival and growth, synapse formation and function, and the ability to phagocytize synapses and myelin debris. While A2, which is induced by ischemia [68], strongly promotes neuronal survival and tissue repair [69; 70]. As our experiments showed, 24-h exposure to SeNrs led to an increase in the baseline expression of genes that encode proteins of the A2 type of reactive astrogliosis. After ischemia/reoxygenation, the effects of SeNrs were observed only for _GFAP_, the level of which increased in astrocytes, however, this increase coincided with the suppression of the expression of _Tnfrsf12A_ involved in inflammation. The role of reactive astrocytes in neuroprotection is difficult to overestimate. A2-reactive astrocytes have been shown to be able to secrete a wide set of neuroprotective molecules. For example, they exert their anti-oxidative functions by secreting molecules such as glutathione [71]. They also secrete a wide array of neurotrophic factors such as glia-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CTNF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), aiding the growth and survival of neurons [72]. Interestingly, reactive astrogliosis occurred simultaneously with an increase in the intracellular content of phosphoinositide 3-kinase (PI3K) in astrocytes both after preincubation with SeNrs and after preincubation with SeNrs followed by ischemia/reoxygenation. It is known that reactive astrocytes displayed pro-inflammatory adaptability through Notch-PI3K-AKT signaling activation in response to inflammatory stimulation [73]. We have previously shown that spherical nanoparticles exert their effect on human glioblastoma cells through the activation of the Ca\({}^{2+}\) signaling system and the opening of Connexin43 (Cx43) hemichannels, which led to the induction of controlled death of cancer cells [74]. At the same time, the same signaling cascade was realized in normal astrocytes, but it had a neuroprotective effect during ischemia [27]. It can be assumed that a similar signaling pathway is also implemented in the case of the use of SeNrs. It is known that mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats [75; 76; 77; 73].