Abstract
The features of changes in the structural and functional characteristics of brain tissue were studied in 60 outbred male Wistar rats during modelling of acute focal cerebral ischemia (AFCI) in the dynamics of treatment with human cryopreserved cord blood serum (CCBS). Electronic and optical microscopic examination of the sensorimotor area of the cerebral cortex was performed. All animals were divided into three groups: the first (control) group consisted of intact rats without trauma and treatment; the second group consisted of animals after modelling AFCI without treatment; third group consisted of rats after modelling AFCI, which were injected by CCBS. Each group consisted of 20 animals. Material for morphological examination was taken after administration of CCBS solution to animals with the model of AFCI at 12, 24, 72 hours and 7th days after the start of the experiment. The average area of perivascular spaces, which is an indicator of vasogenic oedema in rats of group 2 was 45 times higher than in rats of group 1. In contrast, in rats of group 3 with CCBS, this figure was exceeded 37 times. The average area of pericellular spaces, indicating the degree of cytotoxic oedema, in animals of group 2 on the 7th day after AFCI was almost 23 times higher than the results of group 1. This figure in rats of group 3 was increased 20 times compared with data in group 2. Against the background of the use of this drug, there were signs of reactive changes in endothelial cells in the form of an increase in the number of ribosomes and polysomes in the cytoplasm, a decrease in the degree of perivascular oedema of brain tissue by 21.4 %. The surface area of endothelial cells in the zone of AFCI on the 7th day of the experiment in animals that additionally received CCBS was (1483.00±26.48) μm2, which indicates a positive anti-inflammatory effect of the drug. On the 7th day of the experiment in group 3 rats by optical microscopy was found to increase the density of cerebral capillaries compared with group 2, which indicates the stimulation of the restoration of the ultrastructure of damaged capillaries, increase their density, the formation of new capillaries under the components of CCBS.
References
Fujioka T., Kaneko N., Sawamoto K. (2019). Blood vessels as a scaffold for neuronal migration. Neurochem Int., vol. 126, pp. 69–73.
Gianni-Barrera R., Butschkau A., Uccelli A., Certelli A., Valente P., Bartolomeo M. et al. (2018). PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation. Angiogenesis, vol. 21, № 4, pp. 883–900.
Buschmann I., Schaper W. (2000). The pathophysiology of the collateral circulation (arteriogenesis). Journal of Pathology, vol. 190, № 3, pp. 338–342.
Cho Y.L., Hur S.M., Kim J.Y., Kim J.H., Lee D.K., Choe J. et al. (2015). Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation. Journal of Biological Chemistry, vol. 290, № 1, pp. 467–477.
Farrell-Dillon K., Chapple S.J., Alfieri A., Srivastava S., Duchen M. et al. (2016). Focal cerebal ischemia-reperfusion induces the Nrf2 downstream target PPAR gamma in mouse cerebrovascular endothelium. Free Radical Biology and Medicine, vol. 96, pp. S30–S31.
Carmeliet P., Jain R.K. (2011). Molecular mechanisms and clinical applications of angiogenesis. Nature, vol. 473, № 7347, pp. 298–307.
Jetten N., Verbruggen S., Gijbels M.J., Post M.J., De Winther M.P.J. et al. (2014). Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis, vol. 17, № 1, pp. 109–118.
Owen J.L., Mohamadzadeh M. (2013). Macrophages and chemokines as mediators of angiogenesis. Frontiers in Physiology, vol. 4, pp. 24–35.
Guo D.Q., Wang Q.Y., Li C., Wang Y., Chen X. (2017). VEGF stimulated the angiogenesis by promoting the mitochondrial functions. Oncotarget, vol. 8, № 44, pp. 77020–77027.
Kwon Y.W., Heo S.C., Jeong G.O., Yoon J.W., Mo W.M., Lee M.J. et al. (2013). Tumor necrosis factor-alpha-activated mesenchymal stem cells promote endothelial progenitor cell homing and angiogenesis. Biochimica Et Biophysica Acta-Molecular Basis of Disease, vol. 1832, № 12, pp. 2136–2144.
Demir R., Seval Y., Huppertz B. (2007). Vasculogenesis and angiogenesis in the early human placenta. Acta Histochemica, vol. 109, № 4, pp. 257–265.
Albini A., Tosetti F., Benelli R., Noonan D.M. (2005). Tumor inflammatory angiogenesis and its chemoprevention. Cancer Research, vol. 65, № 23, pp. 10637–10641.
Foldvari M., Chen D.W. (2016). The intricacies of neurotrophic factor therapy for retinal ganglion cell rescue in glaucoma: a case for gene therapy. Neural Regeneration Research, vol. 11, № 6, pp. 875–877.
Liu X.F., Ye R.D., Yan T., Yu S.P., Wei L., Xu G.L. et al. (2014). Cell based therapies for ischemic stroke: From basic science to bedside. Progress in Neurobiology, vol. 115, pp. 92–115.
Stefanov O.V. (Eds.). (2001). Doklinicheskiie issledovaniia lekarstvennykh sredstv (metodicheskie rekomendatsii) [Preclinical studies of drugs (guidelines)]. Kyiv: Avitsena, 528 p. [in Russian].
Kolesnyk V.V. (2011). Eksperymentalnyi tromboembolichnyi insult u shchuriv linii Vistar yak variant patofiziolohichnoi modeli hostrykh porushen mikrotsyrkuliatsii za ishemichnym typom [Experimental thromboembolic stroke in Wistar rats as a variant of the pathophysiological model of acute microcirculation disorders by ischemic type]. Patolohiia – Patology, vol. 1, pp. 56–59 [in Ukrainian].
Budantsev A.Yu. (Eds.). (2002). Stereotaksicheskii atlas mozha krysy (frontalnyie secheniia) [Stereotaxic atlas of the rat brain (frontal sections)]. Pushchino: Analiticheskaia mikroskopiia. [in Russian].
McGraw C.P. (1977). Experimental cerebral infarction effects of pentobarbital in Mongolian gerbils. Arch. Neurol., vol. 34, № 6, pp. 334–346.
Ohno K., Ito U., Inaba Y. (1984). Regional cerebral blood flow and stroke index after left carotid artery ligation in the conscious gerbil. Brain Res., vol. 297, № 1, pp. 151–157.
Lychko V.S., Malakhov V.O., Sukach O.M. (2019). Vplyv kriokonservovanoi syrovatky kordovoi krovi na reparatyvni protsesy u tkanyni mozku shchuriv iz hostroiu fokalnoiu tserebralnoiu ishemiieiu [Influence of cryopreserved cord blood serum on reparative processes in rat brain tissue with acute focal cerebral ischemia]. Проблеми кріобіології і кріомедицини – Problems of Cryobiology and Cryomedicine, vol. 29, № 3, pp. 277–290, DOI https://doi.org/10.15407/cryo29.03.277. Retrieved from http://cryo.org.ua/journal/index.php/probl-cryobiol-cryomed/article/view/1554 [in Ukrainian].
Castellano J.M., Mosher K.I., Abbey R.J., McBride A.A., James M.L., Berdnik D. et al. (2017). Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature, vol. 544, № 7651, pp. 488–492, DOI 10.1038/nature22067.
Buzzi M., Versura P., Grigolo B., Cavallo C., Terzi A., Pellegrini M. et al. (2018). Comparison of growth factor and interleukin content of adult peripheral blood and cord blood serum eye drops for cornea and ocular surface diseases. Transfusion and Apheresis Science, vol. 57, № 4, pp. 549–555.
Lin W., Hsuan Y.C., Lin M.T., Kuo T.W., Lin C.H., Su Y.C. et al. (2017). Human umbilical cord mesenchymal stem cells preserve adult newborn neurons and reduce neurological injury after cerebral ischemia by reducing the number of hypertrophic microglia/macrophages. Cell Transplant., vol. 26, № 11, pp. 1798–1810.
Liao S.H., Luo C.X., Cao B.Z., Hu H.Q., Wang S.X., Yue H.L. et al. (2017). Endothelial progenitor cells for ischemic stroke: update on basic research and application. Stem Cells International, vol. 12, pp. 1–12.
Jia L.Y., Zhou X.Y., Huang X.J., Xu X.H., Jia Y.H., Wu Y.T. et al. (2018). Maternal and umbilical cord serum-derived exosomes enhance endothelial cell proliferation and migration. Faseb Journal, vol. 32, № 8, pp. 4534–4543.