EXPRESSION OF THE VASCULAR ENDOTHELIAL GROWTH FACTOR IN THE CEREBRAL CORTEX AT DISTURBANCES OF BLOOD CIRCULATION UNDER CONDITIONS OF PRELIMINARY SENSITIZATION BY BRAIN ANTIGEN AND IMMUNOCORRECTION
DOI:
https://doi.org/10.11603/1811-2471.2018.v0.i2.8513Keywords:
brain ischemia, sensitization, VEGF, imunophane.Abstract
Introduction. The vascular endothelial growth factor (VEGF) is a signaling protein that stimulates angiogenesis and performs trophic functions, including in the nervous system. The indicated growth factor affects the processes of development and migration of nerve cells, their survival.
The aim of the study – to evaluate changes in the expression of VEGF in the cerebral cortex of circulatory disturbances under conditions of preliminary sensitization by brain antigen and immunocorrection.
Results. Observations have shown that sensitization by brain antigen leads to expressive neurodegenerative changes in the sensorimotor cortex and a significant decrease in VEGF expression in neurons. An increase in neurodegenerative and destructive changes in the cerebral cortex and a more significant decrease in the expression of VEGF in neurons characterize embolism of blood vessels of the hemocamcirculatory bed on the background of previous sensitization. In this case, partial recovery after a circulatory disturbance against the background of sensitization occurs more slowly than when the latter do not perform. This can be considering as an immunosupressive suppression of compensatory and restorative processes induced by sensitization. The increase in the number of glial cells observed after the ischemic attack was accompanied by an increase in expression of VEGF.
Immunophane significantly reduces the severity of neurodegenerative changes and a decrease in the expression of VEGF caused by both impaired circulations in the cerebral cortex and sensitization. This can be due either to the direct influence of the immunophane, due to its antioxidant properties, and indirectly, due to the relative activation of T-regulatory cells that act as one of the neuroprotective factors that activated after ischemia.
Conclusions. Sensitization by brain antigen results in expressive neurodegenerative changes in the sensorimotor cortex and a decrease in VEGF expression in neurons.
Embolism of cerebral vessels against the background of previous sensitization, characterized by increased neurodegenerative and destructive changes, an express decrease in VEGF expression and a slowing down of the recovery processes in the cerebral cortex.
Immunophane significantly reduces the severity of neurodegenerative changes and a decrease in the expression of VEGF caused by both impaired circulations in cerebral cortex and sensitization.
References
Rosenstein, J.M., Krum, J.M., & Ruhrberg, C. (2010). VEGF in the nervous system. Organogenesis 6 (2), 107-114.
Licht, T., & Keshet, E. (2013). Delineating multiple functions of VEGF-A in the adult brain. Cellular and Molecular Life Sciences, 70 (10), 1727-1737.
Ma, Y., Zechariah, A., Qu, Y., & Hermann, D.M. (2012). Effects of vascular endothelial growth factor in ischemic stroke. J. Neurosci. Res., 90 (10), 1873-1882.
Licht, T., Eavri, R., Goshen, I., Shlomai, Y., Mizrahi, A., & Keshet, E. (2010). VEGF is required for dendritogenesis of newly born olfactory bulb interneurons. Development, 137 (2), 261-271.
Bao, W.L., Lu, S.D., Wang, H., & Sun, F.Y. (1999). Intraventricular vascular endothelial growth factor antibody increases infarct volume following transient cerebral ischemia. Acta Pharmacol. Sin., 20 (4), 313- 318.
Mackenzie, F., Ruhrberg, C. (2012). Diverse roles for VEGF-A in the nervous system. Development, 20, 1371-1380.
Ruan, L., Wang, B., Zhu, Ge Q., & Jin, K. (2015). Coupling of neurogenesis and angiogenesis after ischemic stroke. Brain Res., 1623, 166- 173. doi:10.1016/j.brainres.2015.02.042.
Yaremenko, L.M., & Hrabovyi, O.M. (2009). Stan populiatsii limfotsytiv pry modeliuvanni porushen krovoobihu u livii pivkuli holovnoho mozku u shchuriv ta yoho korektsiia [State of the population of lymphocytes in the modeling of circulatory disorders in the left hemisphere of the brain in rats and its correction]. Imunolohiia ta alerholohiia – Immunology and Allergology, (1), 40- 44 [in Ukrainian].
Hrabovyi, O.M., & Yaremenko L.M., (2009). Stan kory pivkul holovnoho mozku pry modeliuvanni porushen krovoobihu ta pry korektsii suputnikh zmin imunnoi systemy u shchuriv [State of the cerebral hemispheres in the modeling of circulatory disorders and in the correction of concomitant changes in the immune system in rats]. Naukovyi visnyk Natsionalnoho medychnoho universytetu imeni O.O. Bohomoltsia – Scientific Bulletin of the National Medical University named after O.O. Bohomolets (4), 28-33 [in Ukrainian].
Karaulov, A.V., (2000). Molekulyarno-biologicheskoe obosnovanie primeneniya imunofana v klinicheskoy praktike [Molecular-biological substantiation of the use of imunofan in clinical practice]. Lechashchiy vrach – Attending Physician, (4), 46-47 [in Russian].
Lebedev, V.V., & Novikov, S.A. (2006). Gidrofilnyy geksapeptid imunofan – giperaktivnyy regulyator transportnykh belkov mnozhestvennoy lekarstvennoy ustoychivosti [Hydrophilic hexapeptide imunofan – hyperactive regulator of transport proteins of multiple drug resistance]. Byulleten eksperimentalnoy biologii i meditsyny – Bulletin of Experimental Biology and Medicine, 142 (12), 649-651 [in Russian].
Belozertsev, Yu.A., & Yuntsev, S.V. (2008). Issledovanie neyroprotektornogo i nootropnogo deystviya preparatov pri patologii TsNS [Study of neuroprotective and nootropic action of drugs in the pathology of the central nervous system]. Zabaykalskiy meditsinskiy vestnik – Transbaikal Medical Gazette, (2), 42-45 [in Russian].
Hurn, P.D., & Macrae, I.M. (2000). Estrogen as a neuroprotectant in stroke. J. Cerebral Blood Flow & Metabolism 20, 631-652.
Vyazova, O.E., & Khodzhayeva, Sh.Kh. (Eds.). (1973). Rukovodstvo po immunologii [Guide on immunology]. Moscow: Meditsina [in Russian].
Gannushkina, I.V. (1974). Immunologicheskie aspekty travmy i sosudistykh porazheniy mozga [Immunological aspects of trauma and vascular lesions of the brain]. Мoscow: Meditsina [in Russian].
Hrabovyi, O.M., & Yaremenko, L.M. (2008). Method of modeling of combined vascular-immune brain damage. Ukraine Pat. 36843 [in Ukrainian].
Yaremenko, L.M., Grabovyi, O.O. & Grabovyi, O.M. (2016). Expression of vascular endothelial growth factor in the rat cerebral cortex after blood supply disturbances and immunocorrection of their consequences. Neurophysiology, 48, 354-359. doi:10.1007/s11062-017-9609-y
Plate, K.H., Beck, H., Danner, S., Allegrini, P.R., & Wiessner, C. (1999). Cell type specific upregulation of vascular endothelial growth factor in an MCA-occlusion model of cerebral infarct. J. Neuropathol. Exp. Neurol. 58 (6), 654-666.
Issa, R., Krupinski, J., Bujny, T., Kumar, S., Kaluza, J., & Kumar, P., (1999). Vascular endothelial growth factor and its receptor, KDR, in human brain tissue after ischemic stroke. Lab. Invest., 79 (4), 417-425.
Hai, J., Li, S.T., Lin, Q., Pan, Q.G., Gao, F., & Ding, M.X. (2003). Vascular endothelial growth factor expression and angiogenesis induced by chronic cerebral hypoperfusion in rat brain. Neurosurgery, 53 (4), 963-970; discussion 970-972.
Mărgăritescu, O., Pirici, D., & Mărgăritescu, C. (2010). VEGF expression in human brain tissue after acute ischemic stroke. Rom. J. Morphol. Embryol., 53 (4), 1283-1292.
Liesz, A., Suri-Payer, E., & Veltkamp, C. (2009). Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nature Medicine, 15, 192-199.
Walsh, J.T., Zheng, J., & Smirnov, I. (2014). Regulatory T cells in central nervous system injury: a double-edged sword. J. Immunol., 193 (10), 5013-5022.
