TAU-PROTEIN EXPRESSION IN THE SENSORIMOTOR CORTEX IN THE MODELING OF TRANSIENT ISCHEMIA AND IMMUNOCORRECTION
DOI:
https://doi.org/10.11603/1811-2471.2017.v0.i4.8350Keywords:
brain ischemia, tau protein, immunomodulation.Abstract
Introduction. Ischemia of the brain is accompanied by diffuse damage to the structural elements of the neurons. One of the markers, which demonstrates the functional processes in the nervous system, is a tau-protein.
The aim of the work was to study the peculiarities of tau protein expression in the sensorimotor cortex in conditions of blood supply disturbance and correction of neurodegenerative changes by immunomodulation.
Materials and methods. In the simulation of transient ischemia and correction of neurodegenerative changes with imunofan, an experiment was performed on 150 white mature male rats weighing 260-290 g. Histological, immunohistochemical, morphometric and statistical methods of investigation were used.
Results. Observations have shown that circulatory disturbances in the cerebral cortex lead to an increase in the expression of tau protein in the sensorimotor cortex. The severity of these changes depends on the degree of circulatory disturbance, indirectly confirmed by the presence of changes in the expression of tau protein in the contralateral hemisphere.
The rapid increase in the expression of tau protein in the acute phase after an ischemic attack indicates a disorganization of the cytoskeleton of nerve fibers and, to a certain extent, reflects the phenomena of autoneurotomy. The appearance of tau-protein in the pericarion of neurons can be an indicator of the severity of degenerative processes. The detection of tau-protein in the bodies of gliocytes can be regarded as the phenomena of phagocytosis of decay products.
The use of immunophane, which has a specific neuroprotective effect, has shown its ability to reduce ischemia-induced increased expression of tau protein. This can be explained by the immunoregulatory properties of this peptide (arginyl-aspartyl-lysyl-valyl-tyrosyl-arginine) and its detoxification action, by blocking free-radical processes of peroxidation, by preventing damage to lymphocytes and granulocytes taking part in neurosplenics.
Conclusions. The transient impairment of the blood supply to the sensorimotor cortex of the cerebral hemispheres leads to an increase in the expression of the tau protein, which does not completely recover even 3 months after the ischemic attack. The discirculatory changes in the brain that arise from the mobilization or bandaging of the carotid artery from the side of the operation, as well as those arising in the contralateral hemisphere of the brain, lead to an insignificant, but at a certain stage, statistically significant increased expression of the tau protein.
The use of immunophane in the violation of blood supply to the brain leads to less expressive growth of expression of tau protein in the sensorimotor cortex.
References
Ren, X., Hu, H., Lewis, S.E., Hunsberger, H., Reed, M., & Simpkins, J.W. (2016). Human Tau protects ischemic brain injury. Stroke, 47 (1), A128-A128.
Scholz, T., & Mandelkow, E. (2014). Transport and diffusion of Tau protein in neurons. Cellular and Molecular Life Sciences, 71 (16), 3139-3150.
Bielewicz, J., Kurzepa, J., Czekajska-Chehab, E., Stelmasiak, Z., & Bartosik-Psujek, H. (2011). Does serum tau protein predict the outcome of patients with ischemic stroke? Journal of Molecular Neuroscience, 43 (3), 241-245.
Kadavath, H., Jaremko, M., Jaremko, Ł., Biernat, J., Mandelkow, E., Zweckstetter, M. (2015). Folding of the tau protein on microtubules. Angewandte Chemie International Edition, 54 (35), 10347-10351.
Mishchenko, T.S., Darius, V.I., & Baranova, K.V. (2014). Vzaiemozviazok zapalnykh ta protyzapalnykh markeriv u khvorykh v hostromu periodi mozkovykh insultiv [Interconnection of inflammatory and anti-inflammatory markers in patients with acute period of cerebral stroke]. Ukr. visnyk psykhonevrolohii – Ukrainian Journal of Psychoneurology, 22 (79), 16-18 [in Ukrainian].
Lebedev, V.V., Shelepova, T.M., Stepanov, O.G. (Ed.), Pokrovskogo, V.I. (1998). Imunofan – regulyatornyy peptid v terapii infektsionnykh i neinfektsionnykh bolezney [Immunophane - regulatory peptide in the treatment of infectious and non-infectious diseases]. Moscow [in Russian].
Hurn, P.D. & Macrae, I.M. (2000). Estrogen as a neuroprotectant in stroke. J. Cereb. Dlood. Flow. Metab., 20, 631-652.
Hrabovyi, O.M., Yaremenko, L.M., & Panishyna, N.H. (2008). Sposib modeliuvannia ishemichnoho urazhennia mozku [Method of modeling ischemic brain damage]. Pat. 34604 Ukraina. MPK G09B 23/00. Zaiavnyk i patentovlasnyk Natsionalnyi medychnyi universytet imeni O.O. Bohomoltsia, № u 200805453; opubl. 11.08.2008. Biul. № 15 – Pat. 34604 Ukraine. IPC G09B 23/00 – Applicant and patent holder National Medical University named after O. Bohomolets, № 200805453; has published 08/11/2008. Bull. No. 15 [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 hemisphere in the modeling of circulatory disorders and correction of accompanying changes in the immune system in rats]. Naukovyi visnyk Natsionalnoho medychnoho universytetu imeni O.O. Bohomoltsia – Scientific Journal of O.O. Bohomolets National Medical University, 4, 28-33 [in Ukrainian].
Yaremenko L.M. & Grabovoy, A.N. (2016). Changes in the expression of neurofilament protein in the rat sensorimotor cortex induced by microembolization of blood vessels: Effect of immunomodulation. Neurophysiology, 48 (2), 111-116. Retrieved from http://link.springer.com/article/10.1007/s11062-016-9576-8
Belozertsev, Yu.A. & Yuntsev, S.V. (2008). Issledovaniye neyroprotektornogo i nootropnogo deystviya preparatov pri patologii TSNS [Investigation of neuroprotective and nootropic action of drugs in the pathology of the central nervous system]. Zabaykalskiy meditsinskiy vestnik – Transbaikal Medical Journal, 2, 42-45 [in Russian].
Karaulov, A.V. (2000). Molekulyarno-biologicheskoye obosnovaniye 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].
