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Abstract. The aim of the work was to experimentally study the effect of the created injectable drug basic fibroblast growth factor (bFGF) with the controlled release on morphological changes and indicators of renospecific enzymes in the ischemic kidney (experiment on rabbits). Methods. Studies on the release dynamics of the created bFGF drug were performed in vitro and the study of the induction of bFGF angiogenesis in the model of the chick chorioallantoic membrane of the chicken was performed. The experimental model was performed in 25 rabbits: in 10 rabbits we studied the effect of 1-8 months of "pure ischemia" of the kidney without injection of the drug (control); in 12 rabbits 1 month after the creation of the model of ischemia in the renal parenchyma was injected the prolonged-acting drug bFGF, deposited on our polymeric carrier at a dose of 5 μg (experiment). The reference group consisted of 3 intact rabbits. Histological examinations of renal tissue and morphometric examinations with the determination of vascular coefficient (VC) and interstitial coefficient (IC) were performed. Enzymological indicators of enzyme activity in the homogenate of the renal parenchyma were determined by biochemical methods; statistical analysis was performed. Results. Using chick chorioallantoic membrane as a model it was preliminarily demonstrated that developed injectable prolonged-acting drug bFGF deposited on a polymeric carrier based on cross-linked modified heparin, effectively enhances neoangiogenesis. The results of morphological and morphometric studies with the determination of vascular and interstitial coefficients showed, that the injection of the prolonged-acting drug bFGF in all cases was accompanied by an increased blood supply in the kidneys and neoangiogenesis, which reduced the effects of ischemia. Injection of bFGF at a dose of 5 μg in the model of chronic segmental renal ischemia for 3-4 months completely prevented the development of initial sclerotic and atrophic changes, that developed in the kidney during this period under the influence of chronic ischemia without bFGF. Injection of prolonged-acting bFGF at a dose of 5 μg in the model of chronic segmental renal ischemia for 5-8 months prevented expressed sclerotic and atrophic changes, that developed under the influence of chronic ischemia during this period without the use of bFGF. As a result of biochemical studies, the activation and normalization of indicators of renospecific tubular enzymes in the ischemic kidney under the action of the created experimental drug bFGF were determined. Conclusions. Therapy of ischemic changes in the kidney with the developed injectable long-acting drug bFGF at a dose of 5 µg in the experimental model of chronic ischemia protects the organ from hypoxic damage, has a positive effect on the structural and functional state and metabolism of the kidney, and prevents the development of nephrosclerosis.

Nicotinic acetylcholine receptors of α7 subtype (α7 nAChRs) are involved in regulating cognition, inflammation and cell survival. Neuroinflammation is accompanied by the decrease of α7 nAChRs in the brain and impairment of memory. We show here that α7-/- mice possess pro-inflammatory phenotype and demonstrate worse episodic memory compared to wild-type mice. Previously we reported that mesenchymal stem cells (MSCs) restored episodic memory of lipopolysaccharide-treated wild-type mice. The aim of this study was to examine if MSCs or their soluble factors improve memory of α7-/- mice. The α7-specific signal (ELISA) and α7+ cells (IHC) were found in the brain of α7-/- mice on days 7 and 14 after intravenous injection of α7+ MSCs from either human umbilical cord (hMSCs) or mouse placenta (mMSCs). The intravenously injected MSCs or intraperitoneally injected hMSCs-conditioned medium transiently improved episodic memory of α7-/- mice and decreased cytochrome c release from their brain mitochondria under the effect of Ca2+. Either MSCs or conditioned medium stimulated an IL-6 increase in the brain, which coincided with the improvement of episodic memory. Injections of recombinant IL-6 also improved episodic memory of α7-/- mice accompanied by the up-regulation of α3, α4, β2 and β4 nAChR subunits in the brain. It is concluded that MSCs, injected intravenously, penetrate the brain of α7-/- mice and persist there for at least 2 weeks. They improve episodic memory of mice and make their mitochondria more resistant to apoptogenic influence. One of the soluble factors responsible for the memory improvement is IL-6., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Neuroinflammation is regarded as one of the pathogenic factors of Alzheimer disease (AD). Previously, we showed that mice regularly injected with bacterial lipopolysaccharide (LPS) possessed the AD-like symptoms like episodic memory decline, elevated amounts of amyloid beta (Aβ) peptide (1-42), and decreased levels of nicotinic acetylcholine receptors (nAChRs) in the brain. The use of mesenchymal stem cells (MSCs), which can differentiate into multiple cell types, including neurons, is an attractive idea of regenerative medicine, in particular, for neurodegenerative disorders like AD. In the present study, we aimed to investigate whether pathogenic effect of LPS on the brain and behavior of mice can be prevented or treated by injection of MSCs or MSC-produced soluble factors. Fluorescently-labeled MSCs, injected intravenously, were found in the brain blood vessels of LPS-treated mice. Mice co-injected with LPS and MSCs did not demonstrate episodic memory impairment, Aβ (1-42) accumulation, and nAChR decrease in the brain and brain mitochondria. Their mitochondria released less cytochrome c under the effect of Ca 2+ compared to mitochondria of LPS-only-treated mice. Moreover, MSCs could reverse the pathogenic symptoms developed 3 weeks after LPS injection. Cultured MSCs produced IL-6 in response to LPS and MSCs effect in vivo was accompanied by additional stimulation of both micro- and macroglia. Xenogeneic (human) MSCs were almost as efficient as allogeneic (mouse) ones and regular injections of human MSC-conditioned medium also produced positive effect. These data allow suggesting MSCs as a potential therapeutic tool to cure neuroinflammation-related cognitive pathology.