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Abstract—The aim of this work was to study the involvement of the glutamate, dopamine, and serotonin receptors in the mechanism of the anticonvulsant action of the 4-benzoylpyridine oxime derivative (GIZH-298). After a single corneal exposure to the maximum electric shock (MES) and subsequent tonic–clonic seizures, an increase in the density (Bmax) of NMDA receptors in the hippocampus by 27% and a decrease in the number of mGluII receptors (mGluR2/ 3) by 25% in the prefrontal cortex of the brain of rats were noted. At the same time, the number of 5-HT2A receptors in the prefrontal cortex did not change. GIZH-298 (60 mg/kg) with a single application inhibits convulsive reactions but does not affect the quantitative changes induced by MES in glutamate receptors and does not affect them under normal conditions without MES. In tests on mice, subchronic (5 days) corneal exposure to MES reduced the density (Bmax) of D2 receptors in the striatum by 17% and did not change this parameter in the prefrontal cortex. GIZH-298 (60 mg/kg/5 days) eliminates clonic–tonic convulsions in mice and prevents a decrease in the number of D2 receptors from striatal membranes and also increases their number by 13% in mice without MES in the same structure. The data we obtained indicate significant changes in the functional activity of the NMDA, mGluII, and D2 receptors in the brains of animals that suffered seizures. The anticonvulsant effects of GIZH-298 are accompanied by the restoration of the number of D2 receptors in the striatum. [ABSTRACT FROM AUTHOR]

Abstract—Experiments were carried out on rats of the Krushinsky–Molodkina (KM) strain without sound stimulation (KM-baseline group) and after the development of audiogenic kindling (AuK) in them (KM-AuK group). The control group was rats of the "0" strain, in which convulsions in response to sound were completely absent. AuK was generated using 20 repeated sound stimulation (120 dB). Neurochemical analysis was performed by HPLC/ED in the frontal cortex, hippocampus, hypothalamus, striatum, nucleus accumbens, and brainstem. It was shown that in KM rats AuK leads to the appearance of myoclonic seizures and a decrease in the intensity of generalized convulsive seizures, which is accompanied by a change in the functional activity of the noradrenergic and serotonergic systems of the brain. KM rats in the baseline (without the action of sound and the development of seizures) show a low content of norepinephrine in the hippocampus and hypothalamus, and during the development of AuK, noradrenaline deficiency is observed in the frontal cortex. After the formation of AuK, the serotonin metabolism, which is more intense than in the "0" rats, slows in the hippocampus, nucleus accumbens, and, especially, in the brainstem, and the serotonin deficiency in the striatum disappears. The features of noradrenaline metabolism in KM rats before and after AuK emphasize the important role of the cortex in the development of myoclonic seizures, as well as the possible involvement of the hippocampus and hypothalamus in tonic–clonic seizures. The high functional activity of the serotonergic system, which was revealed in KM rats in a number of brain structures, weakens in the baseline during the development of AuK. The results we obtained demonstrate and confirm the significant role of a brain monoamine imbalance in the genesis of epileptiform seizures in KM rats with genetically determined audiogenic epilepsy and in the development of AuK in them. [ABSTRACT FROM AUTHOR]

Abstract—Extracellular vesicles are macromolecular complexes produced by virtually all types of eukaryotic and prokaryotic cells. According to modern concepts, they allow cells to exchange information, regulate each other's activity and coordinate their actions during the complex processes of development, maintaining homeostasis, tissue regeneration, etc. Extracellular vesicles have a number of unique properties: the ability to accumulate certain types of proteins and nucleic acids, protect them from degradation and ensure their delivery to target cells, which can be used to create biomimetic approaches to the therapy of a wide range of diseases. The composition of vesicles, the preference for docking with a particular cell type, and ultimately their therapeutic potential are very flexible parameters and are highly dependent on the type and properties of the producer cell culture, as well as cultivation conditions. This review gives an idea of the state and prospects of the therapeutic strategies based on the application of extracellular vesicles for neuroprotection and stimulation of brain tissue regeneration after injury, and also considers existing clinical studies which use extracellular vesicles in the field of neurology and neurosurgery. Particular attention in the review is given to new promising approaches to increasing the production of extracellular vesicles, manipulating their contents, and increasing the efficiency of targeted docking in order to increase their therapeutic activity and specificity. [ABSTRACT FROM AUTHOR]

Abstract—This review provides information about the features of cognitive dysfunctions that occur in various diseases and conditions, and data on the history of the creation and characteristic features of nootropics. The review presents the mechanisms of action and the spectrum of pharmacological effects of nootropic drugs from various groups: drugs that affect brain metabolism, neurotransmitter systems (cholinergic, glutamatergic, GABAergic, and others), cerebral vasodilators, neuropeptides and their analogues, antioxidants, membrane protectors, and others. The free radical and mitochondrial concepts of aging and the possibility of using nootropics for the correction of cognitive impairments arising from aging, dementia, and other neurodegenerative diseases are considered. [ABSTRACT FROM AUTHOR]

The method of radioligand binding ex vivo has been used to evaluate the involvement of the ionotropic and metabotropic glutamate and GABA receptors in the mechanism of anticonvulsant action of levetiracetam and the original compound GIZh-290 (2-oxo-4-phenylpyrrolidin-1-yl) acetic acid) in the rat brain. We found that at the peak of lithium-pilocarpine seizures, the B value (the density of specific binding sites) decreases for [H]-SR 95531, [H](-)baclofen, [Н](+)MK-801, and [H]LY 354740 by 30-50% from the control level. The pre-treatment with levetiracetam (600 mg/kg) 40 minutes before pilocarpine kept the number of GABA- and NMDA-type receptors at the control level without affecting the metabotropic receptors. The administration of GIZh-290 (5.0 mg/kg), in contrast, maintained the density of GABA receptors at the control level, while the density of other types of receptors remained decreased at the peak of seizures. Thus, the anticonvulsant effect of levetiracetam and GIZh-290 has different mechanisms. [ABSTRACT FROM AUTHOR]