MEMBRANE-RECEPTOR COMPLEX DYSFUNCTION AS A NEW TARGET FOR THE NEUROTROPHIC THERAPY OF ISCHEMIC STROKE
The aim of the study was the β-adrenergic activity of peripheral blood erythrocyte membranes in the acute period of ischemic stroke (IS).
Peripheral blood erythrocytes are the most informative biological tissue for studying many pathogenetic mechanisms, and the work of their membrane-receptor complex (MRC) can very well reflect the functional state of the whole organism, one of the most important criteria for assessing is the adrenergic activity of cytoplasmic membranes in the pathogenesis of IS.
This study solves the problem of the finding of the features of changes in the adrenoceptors system in the acute period of IS in the dynamics of the treatment of humans cryopreserved cord blood serum (CCBS).
The main scientific results: the obtained results indicate a reduced ability of adrenoceptors (ARs) on erythrocyte membranes to bind blockers due to the desensitisation effect, which is observed from the 1st day of the disease.
In the onset of IS, there is a significant increase in the values of β-adrenergic activity of membranes (β-ARM) of erythrocytes in 2.4 times compared with the control. Maximum levels of the indicator (42.43±3.64 CU) are observed in patients with initially severe disease, which indicates significant stress of the sympathoadrenal system (SAS) in these patients.
On the 10th day of the disease, there was a decrease in β-ARM relative to the values obtained during hospitalisation. Still, comparing the value of the indicator on the 10th day of IS in both groups, there was an apparent, more significant decrease in β-ARM in the 2nd group of patients, which additionally received CCBS.
The use of CCBS contributes to a more pronounced degree of recovery in neurological functions (6.9%) and faster stabilisation of the structure of MRCs in erythrocytes in the form of reducing the values of β-ARM to 16.61±2.86 CU (p<0.05).
The area of practical use of the research results: the results of the study can be used to diagnose and treat of the IS.
An innovative technological product: A comprehensive approach to assess the β-ARM of peripheral blood erythrocytes in patients with IS by determining the degree of changes in osmotic resistance of erythrocytes (ORE) under the action of adrenergic drugs (AD) is informative and can be used to diagnose of IS. The use of neurotrophic factors is a potentially new method of treating this pathology.
Scope of application of the innovative technological product: in the clinical practice of neurological departments for the treatment of patients with strokes
De Oliveira, M. R., Duarte, A. R., Chenet, A. L., de Almeida, F. J. S., Andrade, C. M. B. (2019). Carnosic Acid Pretreatment Attenuates Mitochondrial Dysfunction in SH-SY5Y Cells in an Experimental Model of Glutamate-Induced Excitotoxicity. Neurotoxicity Research, 36 (3), 551–562. doi: http://doi.org/10.1007/s12640-019-00044-8
Zhang, Z., Yan, J., Shi, H. (2016). Role of Hypoxia Inducible Factor 1 in Hyperglycemia-Exacerbated Blood-Brain Barrier Disruption in Ischemic Stroke. Neurobiology of Disease, 95, 82–92. doi: http://doi.org/10.1016/j.nbd.2016.07.012
Bivard, A., Parsons, M. (2018). Tissue is more important than time: insights into acute ischemic stroke from modern brain imaging. Current Opinion in Neurology, 31 (1), 23–27. doi: http://doi.org/10.1097/wco.0000000000000520
Lees, K. R., Bornstein, N., Diener, H.-C., Gorelick, P. B., Rosenberg, G., Shuaib, A. (2013). Results of Membrane-activated Chelator Stroke Intervention Randomized Trial of DP-b99 in Acute Ischemic Stroke. Stroke, 44 (3), 580–584. doi: http://doi.org/10.1161/strokeaha.111.000013
Boehme, A. K., McClure, L. A., Zhang, Y., Luna, J. M., Del Brutto, O. H., Benavente, O. R., Elkind, M. S. V. (2016). Inflammatory Markers and Outcomes After Lacunar. Stroke Levels of Inflammatory Markers in Treatment of Stroke Study. Stroke, 47 (3), 659–667. doi: http://doi.org/10.1161/strokeaha.115.012166
Khoshnam, S. E., Winlow, W., Farzaneh, M., Farbood, Y., Moghaddam, H. F. (2017). Pathogenic mechanisms following ischemic stroke. Neurological Sciences, 38 (7), 1167–1186. doi: http://doi.org/10.1007/s10072-017-2938-1
Zis, O., Zhang, S., Dorovini-Zis, K., Wang, L., Song, W. (2014). Hypoxia Signaling Regulates Macrophage Migration Inhibitory Factor (MIF) Expression in Stroke. Molecular Neurobiology, 51 (1), 155–167. doi: http://doi.org/10.1007/s12035-014-8727-4
Beneduci, A., Cosentino, K., Romeo, S., Massa, R., Chidichimo, G. (2014). Effect of millimetre waves on phosphatidylcholine membrane models: a non-thermal mechanism of interaction. Soft Matter, 10 (30), 5559–5567. doi: http://doi.org/10.1039/c4sm00551a
Gapeyev, A. B., Sokolov, P. A., Chemeris, N. K. (2001). Response of membrane-associated calcium signaling systems of the cell to extremely low-frequency external signals with different waveform parameters. Electro- and Magnetobiology, 20 (1), 107–122. doi: http://doi.org/10.1081/jbc-100103163
Hama, S., Murakami, T., Yamashita, H., Onoda, K., Yamawaki, S., Kurisu, K. (2016). Neuroanatomic pathways associated with monoaminergic dysregulation after stroke. International Journal of Geriatric Psychiatry, 32 (6), 633–642. doi: http://doi.org/10.1002/gps.4503
Hausdorff, W. P., Caron, M. G., Lefkowitz, R. J. (1990). Turning off the signal: desensitization of β‐adrenergic receptor function. The FASEB Journal, 4 (11), 2881–2889. doi: http://doi.org/10.1096/fasebj.4.11.2165947
Johnson, J. A., Terra, S. G. (2002). Beta-adrenergic receptor polymorphisms: Cardiovascular disease associations and pharmacogenetics. Pharmaceutical Research, 19 (12), 1779-1787. doi:–http://doi.org/10.1023/a:1021477021102
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, 11 (6), 875–877. doi: http://doi.org/10.4103/1673-5374.184448
Liu, X., Ye, R., Yan, T., Yu, S. P., Wei, L., Xu, G. et. al. (2014). Cell based therapies for ischemic stroke: From basic science to bedside. Progress in Neurobiology, 115, 92–115. doi: http://doi.org/10.1016/j.pneurobio.2013.11.007
Patel, R. A. G., McMullen, P. W. (2017). Neuroprotection in the Treatment of Acute Ischemic Stroke. Progress in Cardiovascular Diseases, 59 (6), 542–548. doi: http://doi.org/10.1016/j.pcad.2017.04.005
Tsirkin, V. I., Gromova, M. A., Kolchina, D. A. (2008). Otsenka adrenoreaktivnosti eritrotsitov, osnovannaya na sposobnosti povyishat skorost agglyutinatsii eritrotsitov. Fundamentalnyie issledovaniya, 7, 59–60.
Malakhov, V. O., Nosatov, A. V., Fisun, A. I., Sirenko, S. P., Bilous, O. I. (2016). Pat. No. 108233 UA. Sposib kompleksnoho likuvannia porushen mozkovoho krovoobihu. MPK: G01N 33/49 (2006.01), A61B 5/145 (2006.01). No. u 201600029; declareted: 04.01.2016; published: 11.07.2016, Bul. No. 13.
Copyright (c) 2020 Volodymyr Lychko
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