Hubenia O. Clinical, diagnostic and pathogenetic significance of gene proliferation and apoptosis in patients with ischemic stroke.

The thesis is devoted to the improvement of diagnostic and treatment strategy of patients with ischemic stroke by comprehensive clinical and paraclinical studies, and studies of gene expression features that play an important role in cell proliferation and apoptosis under ischemic conditions in the nervous tissue. In the paper the theoretical generalization and a new solution to the practical aspects of the scientific issue of ischemic stroke: Determining risk factors, the clinical course, and the main pathogenic mechanisms of ischemic stroke based on a comprehensive study of clinical and neurological data, results of molecular and biochemical, instrumental and neuroimaging methods, as well as, improved pharmacological correction. By creating an experimental model of hypoxic-ischemic damage of the nervous tissue, it has been shown, for the first time, that the expression of genes, that regulate processes of cell proliferation and apoptosis (VEGF, PFKFB, NPDC1, SLC1A1 and BDNF) in cell culture of U87 glioma line, changes under the conditions of ischemia and it has been shown that the effect of hypoxia and ischemia on the expression of the studied genes in glioma cell culture greatly depends upon the function of sensory enzyme ERN-1. It has, also, been shown that VEGF gene expression, which is involved in the regulation of angio- and neurogenesis, is increased in brain cell cultures under the conditions of ischemia when treated with citicoline. We have justified the need for citicoline use in patients with ischemic stroke to improve the effectiveness of treatment and to prevent progression of neurologic deficit.