###### Abstract  
The search for new molecular targets whose modulation can reduce nerve cell dysfunction and neuronal death during ischemic damage is one of the most significant issues in both fundamental and clinical neurobiology. Various kinase enzymes are often considered to be such promising targets since they are involved in key molecular cascades that regulate cell adaptation to stress factors. Our work is devoted to the study of the role of two kinases--SRC and IKK\(\beta\)--in maintaining the neural networks' functional activity under a hypoxic condition in vivo and in vitro. SRC kinase is a cytoplasmic non-receptor protein tyrosine kinase. It is involved in the regulation of cell proliferation and differentiation; its expression in nerve cells changes during hypoxia. IKK\(\beta\) kinase is involved in the regulation of the activity of the transcription factor NF-\(\kappa\)B, which is a pleiotropic regulator of many cellular signaling pathways. We have shown that blockade of SRC and IKK\(\beta\) kinases by selective inhibitors maintains cell viability in modeling hypoxic damage in vitro but does not allow for the preservation of the bioelectrical activity of neurons. Studies in vivo have shown the neuroprotective effect of SRC but IKK\(\beta\) kinase inhibition in the modeling of cerebral ischemia in mice. kinases; SRC; IKK\(\beta\); primary hippocampal cultures; bioelectrical neural network activity; hypoxia; neuroprotection; ischemia +
Footnote †: journal: Medical Imaging in Vitro and In Vivo  
Previously, our research group screened the effect of more than 100 different neuronal kinases' inhibitors on the viability of nerve cells in primary hippocampal cultures under physiological conditions and in the modeling of glucose deprivation in vitro [8]. In vitro, we identified and studied in more detail kinases whose blockade had a neuroprotective effect that was manifested in the effective maintenance of the nerve cell viability under glucose deprivation and hypoxic conditions at the level of intact cultures. However, studies of calcium activity showed that the blockade of these kinases did not allow for the maintenance of the collective functional calcium dynamics [8; 9]. The present work is a further continuation of this comprehensive study. We focused on a deeper study of the effects that blockade of SRC and IKK\(\beta\) kinases has on neural network activity, for which we studied spontaneous neural network bioelectric activity using multielectrode arrays and also verified the results obtained in cell cultures regarding the neuroprotective effect of inhibition of these kinases in studies in vivo. The SRC kinase family is an important subgroup of cytoplasmic tyrosine kinases that are not receptors on the cell membrane. Kinases of this family are widely distributed in the brain [10]. SRC kinase was the first non-receptor tyrosine kinase that was described. The release of different bioactive molecules, including glutamate, cytokines, thrombin, oxyhemoglobin, and ROS during hypoxia can activate SRC. Activated SRC modulates the release of proapoptotic molecules from mitochondria into the cytosol, which leads to the activation of caspases 3, 7, and 9, followed by DNA fragmentation and cell death. It can be assumed that SRC inhibition will become an effective treatment for ischemic brain damage in the future [11]. Another interesting kinase is IKK\(\beta\). In ischemia, this kinase can activate the transcription factor NF-kB, which plays an important role in the adaptation of the central nervous system to ischemic damage by regulating the expression of target genes and the activity of other molecular pathways involved in the development of ischemic stroke. Meanwhile, various studies indicate that NF-kB can play both positive and negative roles in the regulation of ischemic resistance [12]. Currently, there is insufficient data on the neuroprotective effects of SRC and IKK\(\beta\) kinase inhibition. Moreover, there are no studies on the influence of these blockers on the functioning of the brain's neural networks.