Since the discovery of the neuron-specific protein by Moore and McGregor in 1965, tens of thousands of studies have investigated the basic and applied significance of neuron-specific enolase (NSE). This promising biomarker, according to many researchers, has not found widespread use in clinical practice, particularly in acute cerebrovascular accidents. Moreover, the several studies refuting the usefulness of serum NSE measurement in critically ill patients leads us to consider the reasons for such contradictory conclusions. In this article, we have analyzed the main directions in the study of NSE and expressed our perspective on the reasons for the contradictory results and the difficulties in implementing the results of these studies in clinical practice. In our opinion, the method of the enzyme-linked immunosorbent assay (ELISA) used in the majority of the studies is inappropriate for the evaluation of NSE as a marker of central nervous system damage, because it does not allow for the differentiation of heterodimers of enolases and the assessment of the enzymatic activity of this group of enzymatic proteins. Therefore, the methodological approach for the evaluation of NSE (γγ-enolase) as a biomarker needs to be elaborated and improved. Furthermore, the specificity of the applied research methods and the appropriateness of the continued use of the term “neuron-specific enolase” must be addressed.

The increased plasma levels of von Willebrand factor (VWF) in patients with COVID-19 was reported in many studies, and its correlation with disease severity and mortality suggest its important role in the pathogenesis of thrombosis in COVID-19. We performed histological and immunohistochemical studies of the lungs of 29 patients who died from COVID-19. We found a significant increase in the intensity of immunohistochemical reaction for VWF in the pulmonary vascular endothelium when the disease duration was more than 10 days. In the patients who had thrombotic complications, the VWF immunostaining in the pulmonary vascular endothelium was significantly more intense than in nonsurvivors without thrombotic complications. Duration of disease and thrombotic complications were found to be independent predictors of increased VWF immunostaining in the endothelium of pulmonary vessels. We also revealed that bacterial pneumonia was associated with increased VWF staining intensity in pulmonary arterial, arteriolar, and venular endothelium, while lung ventilation was an independent predictor of increased VWF immunostaining in arterial endothelium. The results of the study demonstrated an important role of endothelial VWF in the pathogenesis of thrombus formation in COVID-19.

Vascular endothelial growth factors (VEGFs) are important regulators of angiogenesis, neuroprotection, and neurogenesis. Studies have indicated the association of VEGF dysregulation with the development of neurodegenerative and cerebrovascular diseases. We studied the changes in serum levels of VEGF-A, VEGFR-1, and VEGFR-2 in patients at various phases of ischemic and hemorrhagic strokes. Quantitative assessment of VEGF-A, VEGFR-1, and VEGFR-2 in serum of patients with hemorrhagic or ischemic stroke was performed by enzyme immunoassay in the hyper-acute (1–24 h from the onset), acute (up to 1–7 days), and early subacute (7 days to 3 months) phases of stroke, and then compared with the control group and each other. Results of our retrospective study demonstrated different levels of VEGF-A and its receptors at various phases of ischemic and hemorrhagic strokes. In ischemic stroke, increased VEGFR-2 level was found in the hyper-acute (p = 0.045) and acute phases (p = 0.024), while elevated VEGF-A and reduced VEGFR-1 levels were revealed in the early subacute phase (p = 0.048 and p = 0.012, respectively). In hemorrhagic stroke, no significant changes in levels of VEGF-A and its receptors were identified in the hyper-acute phase. In the acute and early subacute phases there was an increase in levels of VEGF-A (p < 0.001 and p = 0.006, respectively) and VEGFR-2 (p < 0.001 and p = 0.012, respectively). Serum levels of VEGF-A and its receptors in patients with hemorrhagic and ischemic stroke indicate different pathogenic pathways depending on the phase of the disease.

The leading factors of post-stroke disability are motor disorders and cognitive dysfunctions. The aim of the study was to identify and provide a rationale for the variable early cognitive dysfunction in right and left hemispheric damage in patients with acute stroke. The study included 80 patients diagnosed with ischemic stroke. All patients were assessed for cognitive status, depression, fatigue and anxiety. For objectification, the method of evoked potentials (P300) and neuroimaging were used. Our findings revealed distinguishing features of cognitive dysfunction and identified a combination of the most informative markers characteristic of right and left hemispheric damage in patients with acute ischemic stroke. In patients with damage to the left hemisphere, a predominance of dysregulation syndrome (decrease in executive function and attention) was revealed, accompanied by various disorders such as severe anxiety and fatigue. The causes of this cognitive dysfunction may be directly related to stroke (damage to subcortical structures), as well as to a preexisting reduction in higher mental functions associated with age and vascular conditions. Cognitive impairments in patients with lesions of the right hemisphere were characterized by polymorphism and observed in the mental praxis, speech (with predominant semantic component) and abstract thinking domains. They are closely linked to each other and are more related to the lateralization of the lesion and preexisting neurodegeneration than to the localization of the ischemic lesion. The study of P300-evoked potentials is a good tool for confirming cognitive dysfunction. The latent period of the P300 wave is more sensitive to neurodegeneration, while the amplitude factor characterizes vascular pathology to a greater extent. The results of the study provide a rationale for a comprehensive assessment of lateralization, stroke localization, underlying diseases, neurophysiological parameters and identified cognitive impairments when developing a plan of rehabilitation and neuropsychological measures aimed at cognitive and emotional recovery of patients both in the acute phase of ischemic stroke and when selecting further personalized rehabilitation programs.

The purpose of the study was to evaluate the clinical significance of CNS biological markers in an ischemic stroke.Materials and methods. Blood serum biomarkers of CNS were assayed by ELISA in patients suffering from cerebrovascular disorders of ischemic origin. Neuron-specific enolase, brain-derived neutrophic factor (BDNF), glial-derived neutrophic factor (GDNF), protein S-100 total (ɑβ–ββ), sialyl carbohydrate antigen (KL-6), vascular endothelial growth factor, and superoxide dismutase were analyzed. All tests were carried out using automatic microplate immunoassay analyzer Immunomat TM. The study included 43 patients of 50 to 80 years of age, suffering from cerebrovascular disorders; among them there were 24 women and 19 men. Blood serum biomarkers of CNS were assayed within the first 3–6 hours, and on week 2, 3, and 4 from onset of the disease. The control group consisted of 20 volunteers (apparently healthy donors). Statistical analysis was carried out using non-parametrical Mann–Whitney test. Results were considered as significant at P 0.05.Results. During the pre-necrotic and early necrotic period, higher neuron-specific enolase, protein S-100, superoxide dismutase, and lower brain-derived neutrophic factor and glial-derived neutrophic factor were observed, reflecting structural brain alterations due to disturbed circulation. At later follow-up time-points, BDNF, GDNF, VEGF, and KL-6 increased evidencing activated CNS regeneration processes.Conclusion. The content of biological markers in blood serum of ischemic stroke patients reflects the disease stages, which helps managing the CNS regeneration processes.

Despite the enormous interest in COVID-19, there is no clear understanding of the mechanisms underlying the neurological symptoms in COVID-19. Microglia have been hypothesized to be a potential mediator of the neurological manifestations associated with COVID-19. In most existing studies to date, morphological changes in internal organs, including the brain, are considered in isolation from clinical data and defined as a consequence of COVID-19. We performed histological immunohistochemical (IHC) studies of brain autopsy materials of 18 patients who had died from COVID-19. We evaluated the relationship of microglial changes with the clinical and demographic characteristics of the patients. The results revealed neuronal alterations and circulatory disturbances. We found an inverse correlation between the integral density Iba-1 (microglia/macrophage-specific marker) IHC staining and the duration of the disease (R = −0.81, p = 0.001), which may indicate a reduced activity of microglia and do not exclude their damage in the long-term course of COVID-19. The integral density of Iba-1 IHC staining was not associated with other clinical and demographic factors. We observed a significantly higher number of microglial cells in close contact with neurons in female patients, which confirms gender differences in the course of the disease, indicating the need to study the disease from the standpoint of personalized medicine.