Lushnikova I. Intercellular interactions and endogenous mechanisms of neuroprotection in the hippocampal model of ischemic damage

The dissertation presents the results of a comprehensive study of various types of hippocampal cells. The intercellular interactions and some endogenous mechanisms of neuroprotection have been studied for ischemic damage in vitro model using hippocampal organotypic and cell cultures, as well as oxygen-glucose deprivation (OGD). It is revealed that when pyramidal neurons are damaged and die, interneurons retain their viability, and astro-and microglial cells are activated. Changes in the plasticity of excitatory and inhibitory synapses and glial processes in the most sensitive CA1 area cultured slices were analyzed in the initial period after OGD. It was revealed that the inhibitory GABA-ergic interneurons are acetylcholine-sensitive and interconnected by electrotonic contacts. These properties can cause their OGD-resistance to a great extent. The damage of pyramidal neurons may be associated with the glycine receptors reduction in OGD. It is shown that neuronal cell adhesion molecules (NCAM) are involved in synaptic plasticity disorders. Synaptic transmembrane protein presenilin-1 and synaptotagmin-1 coordinate the effectiveness of synaptic transmission. The important role of hypoxia-induced factors (HIF) in maintaining the viability of nerve cells has been shown in OGD. Neuroprotective effects of anoxic preconditioning are associated with an increased level of HIF expression in neurons and is mediated by the stabilization of Са2+ATPases. The functional interrelationship of NCAM- and HIF-mediated mechanisms has been identified. The neuroprotective effect of multipotent mesenchymal stromal stem cells was shown in contact and non-contact cocultivation with slices in OGD. The molecular mechanisms of ischemic injury may be new pharmacological targets for brain ischemia. Keywords: hippocampus, ischemic damage in vitro, neuroprotection.