The thesis aims to study the clinical and neurological characteristics of patients with acute ischemic stroke (IS), as well as neuroimaging, immunological, biochemical, biophysical, histological and pharmacotherapeutic parameters of their brain tissue, and to provide theoretical justification and a new solution to the relevant scientific angioneurologic issue of determining the pathogenetic role of acute dysfunction of a membrane-receptor cell complex in functional development of the sympathetic-adrenal and immune systems, as well as to clinically and experimentally prove the possibility of stimulating the neuroplasticity and secondary angiogenesis processes in drug therapy dynamics. The experimental part of the thesis was based on a histological study of structural and morphological characteristics of brain tissue of 60 outbred white male Wistar mice with modelled acute focal cerebral ischemia (AFCI) in dynamics of using the cryopreserved cord blood serum (CCBS). The clinical part of the study included examining 378 IS patients; among them, 350 patients were selected upon screening for compliance with inclusion/exclusion criteria. A set of methods was used to achieve the study’s objective, including clinical-anamnestic, clinical-neurological, neuroimaging, biophysical, biochemical, immunological, histological medical-statistical analysis. As a result, it was found that additional use of CCBS as soon as the 7th day after AFCI modelling led to a decrease in the perivascular oedema area by 21.4 %. At the same time, there was an increase in cerebral capillaries density and restoration of ultrastructure damaged, indicating stimulation of secondary angiogenesis by the CCBS.
In irreversibly damaged neurons, the cell body was destroyed, lysis of nuclei was recorded, diffusely scattered clumps of chromatin were found. As a result, the alteration index increased 4.57 times. An increase in the frequency of glial cells paired location was a sign of hypoxia, which led to the rise in perineuronal satellite index by 3.62 times. The degree of dependence of clinical and neurological signs of acute IS on the sympathetic-adrenal system’s functional condition was determined according to the data of β-adrenergic membrane reactivity (β-ARM) of peripheral blood erythrocytes in the treatment dynamics and their relation to membrane-receptor dysfunction. Changes in dielectric properties of peripheral blood erythrocytes of patients while in vitro exposure to adrenal reactive drugs, as well as in the system of trigger pro-inflammatory (interleukin (IL)-6, tumour necrotizing factor-α) and anti-inflammatory cytokines (IL-4, IL-10) in drug therapy dynamics were revealed. New causal relations have been defined between the levels of pro- and anti-inflammatory cytokines, β-ARM of erythrocytes and dielectric properties. Prognostic significance of the imbalance degree in the immune system, changes in structural and morphological characteristics of brain tissue, dielectric properties and β-ARM of erythrocytes in IS pathogenesis was determined, followed by the development of new diagnostic criteria for the disease severity. Based on the data obtained, a complex therapy program for patients with acute IS was scientifically substantiated, developed, tested and put into practice using cryopreserved human cord blood serum and considering the leading pathogenetic and pharmacotherapeutic features.
Implementation of this program has significantly improved the neurological care, as well as life quality of post-stroke patients.
