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Information × Registration Number 0220U000039, 0118U002332 , R & D reports Title Functioning of blood-brain barrier and neurotransmission under inflammatory state: role of immune and haemostatic systems in neuroinflammation. popup.stage_title Head Kasatkina Ludmila Oleksandrivna, Registration Date 09-01-2020 Organization A.V.Palladin Institute of Biochemistry of National Academy of Sciences popup.description2 The study of neurotransmission and the functioning of the blood-brain barrier under inflammatory condition were carried out on the model of lipopolysaccharide (LPS)-induced inflammation and neuroinflammation, and the migration of immune cells into the brain was studied under conditions of experimental autoimmune encephalitis. The state of astroglia was assessed (by the content of a specific marker of astrocytes GFAP), the content of inducible NO synthase (iNOS), Iba1 and ZO-1 proteins in the hippocampus and the prefrontal cortex of mice were determined. The metalloproteinase activity in the prefrontal cortex and hippocampus was studied, which characterizes remodelling of the intercellular matrix, in particular the blood-brain barrier, during inflammation. As a result of the studies, the components of the haemostatic system (protein C, prothrombin and fibrin degradation products) were analyzed, the activity and/or content of which change with inflammation and can cause structural and functional changes in the vascular endothelium and blood-brain barrier. It was shown that treatment with levetiracetam, the specific modulator of synaptic vesicle SV2A protein, is able to reduce the in vivo generation of ?-amyloid in the hippocampus of rats with neuroinflammation, which allows considering such strategy of suppressing neuronal activity for neuroprotection under neuroinflammation. In collaboration with the Otto-Loewi Research Center (Medical University of Graz, Austria): 1) Subpopulations of leukocytes that actively migrate through the blood-brain barrier in vivo under inflammation were identified and the effect of anti-inflammatory therapy with N-stearoylethanolamine on this process was evaluated. 2) In vivo studies of the action of the components of the endocannabinoid system and N-stearoylethanolamine on neurotransmission under neuroinflammation were continued in vitro and a comparative analysis of the studied processes was carried out. It was shown that endocannabinoids and N-stearoylethanolamine affect the amplitude of stimulated exocytosis in neurons of the prefrontal cortex and hippocampus in different ways, and the increase of the amplitude of exocytosis by N-stearoylethanolamine in vitro is due to its effect on neuronal survival. The protective effect of the antiepileptic drug levetiracetam and the active form of vitamin D3 (1,25(OH)2D3) under conditions of neuroinflammation was revealed and the effect of these compounds on secretion in neurons during inflammation was evaluated. Cholecalciferol and the VDR receptor were shown to play an important role in regulating the balance of pro/anti-inflammatory responses in the brain during systemic inflammation. Along with this, vitamin D3 deficiency in experimental animals causes pro-inflammatory changes and reduces stimulated secretion in presynapses. Cholecalciferol, as well as the lipid mediator N-stearoylethanolamine, can increase the survival of neurons, which affects the parameters of secretory activity in experiments. Experimental data indicate that active cell migration through the blood-brain barrier under LPS-induced systemic inflammation is not always associated with an increase in the activity and/or content of matrix metalloproteinases in the brain. Even with high doses of LPS, no significant changes in the activity of matrix metalloproteinases were observed, which, however, did not interfere with the regulated migration of immune cells under inflammatory state. At the same time, in response to the induction of inflammation in mice, an increase in the expression levels of ZO-1 protein is observed, which causes compensatory strengthening of tight junctions of the blood-brain barrier. Product Description popup.authors Гудзь Єгор Анатолійович Гузик Михайло Михайлович Лісаковська Ольга Олександрівна Чернишенко Володимир Олександрович popup.nrat_date 2020-04-02 Close