DYNAMICS OF INDICATORS OF THE ENDOTHELIUM MORPHOFUNCTIONAL STATE OF THE BRAIN MICROCIRCULATORY BED VESSELS IN RATS WITH NITRITE-INDUCED ALZHEIMER'S TYPE DEMENTIA ON THE BACKGROUND OF MESENCHYMAL STEM CELL ADMINISTRATION OR WITHOUT IT

DYNAMICS OF INDICATORS OF THE ENDOTHELIUM

  • Yevgeniya Zorenko Kharkiv National Medical University, Department of Physiological Pathology

Sažetak


Objective. The aim of this study was to assess the vascular endothelium morphofunctional state of the brain microcirculatory bed in rats with nitrite-induced Alzheimer's type dementia on the background of stem cells administration or without it.

Methods. 14 days after the experiment end, the endothelin-1, VEGF-A, eNOS, von Willebrand factor were determined in blood serum by the enzyme immunoassay and photometric methods in rats with a model of nitrite-induced dementia (14 and 28 days of sodium nitrite intraperitoneal introduction) with and without mesenchymal stem cells (MSCs) administration. The brain slices were stained according to the Einarson’s method and immunohistochemically by staging the reaction with antibodies to VEGF.

Results. With an increase in the sodium nitrite administration period, the damage degree of brain capillaries and neurons increases, dystrophy of “surviving” neurons develops and ability to produce VEGF decreases. After 14 days of "regeneration period" in groups without  MSCs administration, further stimulation of VEGF production by endotheliocytes, cortex and hippocampus neurons  of varying degrees is observed. In groups where stem cells were introduced, the number of capillaries increases, with endothelial hyperplasia in some places.

Conclusion. In animals with nitrite-induced dementia, dose-dependent damage to the endothelium of the capillary bed is noted. From the first day damage the vascular regeneration can be proved by VEGF expression. The stem cells administration more effectively stimulates capillary regeneration, as evidenced by a noticeable increase of the brain capillaries number.

Reference

1 - De la Monte S.M., Neusner A., Chu J., Lawton M. (2009) Epidemilogical trends strongly suggest exposures as etiologic agents in the pathogenesis of sporadic Alzheimer's disease, diabetes mellitus, and non-alcoholic steatohepatitis. J Alzheimers Dis 17(3):519-29.
2 - Fish K.M., Hajjar R.J. (2015) Mesenchymal Stem Cells & Endothelial Function. EBioMedicine 2(5): 376–77.
3 - Gorbach T.V., Nakonechna O.A., Tkachenko A.S., Shcholok T.S., Onikova A.O. (2018) Levels of thyroid hormones and indices of energy metabolism in the cerebral cortex of rats with experimental Alzheimer’s disease. Neurophysiology 50 (3):159–65.
4 - Hardy J.A., Higgins G.A. (1992) Alzheimer's disease: The amyloid cascade hypothesis. Science 256(5054): 184–85.
5 - Huang L., Jia J., Liu R. (2013) Decreased serum levels of the angiogenic factors VEGF and TGF-β1 in Alzheimer's disease and amnestic mild cognitive impairment. Neuroscience letters 550: 60–3.
6 - Kapasi A., Schneider J.A. (2016) Vascular contributions to cognitive impairment, clinical Alzheimer's disease, and dementia in older persons. Biochimica et biophysica acta 1862(5): 878–86.
7 - Kaporskij L.N. Opticheskaja plotnost'. In Prohorov AM (ed) Fizicheskaja jenciklopedija. Vol.3. Moscow: Bol'shaja Rossijskaja jenciklopedija. 1992.
8 - Kuznecova A.S., Gozhenko A.I., Kuznecova E.S., Shuhtin V.V., Kuznecova E.N., Kuznecov S.G. Jendotelij. Fiziologija i patologija : monografija. Odessa: Fenіks. 2018
9 - Lukyanova Y.M. (2019) Influence of Chronic Administration of Sodium Nitrite on Morphofunctional State of Brain in Rats. Ukr. ž. med. bìol. sportu 4, 6(22): 52-9.
10 - Lukyanova Y.M., Gubina-Vakulyck G.I., Gorbach T.V. (2020) Morfofunkcіonal'nij stan sudin golovnogo mozku u shhurіv z demencієju al'cgejmerovs'kogo tipu sudinnogo pohodzhennja. From experimental and clinical pathophysiology to the achievements of modern medicine and pharmacy : abstracts of the II scientific-practical conference of students and young scientists with international participation. Kh.: NUPh: p.128-29
11 - Nelson A.R., Sweeney M.D., Sagare A.P., Zlokovic B.V. (2016). Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. Biochim Biophys Acta 1862 (5): 887-900.
12 - Nikolayeva O.V., Pavlova O.O., Lukyanova Y.M., Gubina-Vakulik G.I., Gorbach T.V. (2020) Sposib modelyuvannya dementsiyi altsgeymerivskogo typu u shchuriv (UA Patent No. 141759) UA Kharkiv National medical University.
13 - Okabe K., Fukada H., Tai-Nagara I., et al. (2020) Neuron-derived VEGF contributes to cortical and hippocampal development independently of VEGFR1/2-mediated neurotrophism. Developmental biology 459(2): 65–71. https://doi.org/10.1016/j.ydbio.2019.11.016
14 - Parodi-Rullán R., Sone J.Y., Fossati S. (2019) Endothelial Mitochondrial Dysfunction in Cerebral Amyloid Angiopathy and Alzheimer’s Disease. Journal of Alzheimer's disease 72(4): 1019–39.
15 - Pluta R., Jabłoński M., Ułamek-Kozioł M., Kocki J., Brzozowska J., Januszewski S., Furmaga-Jabłońska W., Bogucka-Kocka A., Maciejewski R., Czuczwar S.J. (2013) Sporadic Alzheimer's disease begins as episodes of brain ischemia and ischemically dysregulated Alzheimer's disease genes. Mol Neurobiol 48(3): 500-15.
16 - Pyatikop V., Msallam M., Shchegelskaya E., Kutovoy I., Gubina-Vakulik G. (2014) Migration features of labeled bone marrow mesenchymal stem cells in rats with modeled Parkinson-like syndrome. Ukrainian Neurosurgical Journal 3: 42-8.
17 - Romaniuk A., Gyryavenko N., Lyndin M., Piddubnyi A., Sikora V., Korobchanska A. (2016) Primary cancer of the fallopian tubes: histological and immunohistochemical features. Folia medica Cracoviensia 4: 71-80
18 - Savitskiy I.V., Gorbach T.V., Miastkovskaja I.V., Grigoriev P.E., Yakushkin E.Y., Sliusar A.A. (2016) Dynamics endothelial dysfunction nitrate under the influence of load. Journal of Education, Health and Sport 6(2): 337-48.
19 - Shaughness M., Acs D., Brabazon F., Hockenbury N., Byrnes K.R. (2020) Role of Insulin in Neurotrauma and Neurodegeneration: A Review. Front Neurosci 14:547175. .
20 - Tong M., Longato L., de la Monte S.M. (2010) Early limited nitrosamine exposures exacerbate high fat diet-mediated type 2 diabetes and neurodegeneration. BMC Endocr Disord 10:4
21 - Verclytte S., Lopes R., Lenfant P., et al. (2016) Cerebral hypoperfusion and hypometabolism detected by arterial spin labeling MRI and FDG‐PET in early‐onset Alzheimer's disease. J. Neuroimaging 26: 207–12.
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2021/09/01
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