Correlation Analysis between NETosis Biomarkers and Peripheral Immune Cells in a Preclinical Model of Ischemic Stroke

Neutrophil extracellular traps formation (NETosis) facilitates thrombosis and contributes to reperfusion resistance - a major challenge encountered during the treatment of acute ischemic stroke. The effect of acute stroke on plasma NETosis biomarkers remains unclear. In this study, young adult C57BL/6 wildtype (WT) mice were subjected to acute brain ischemia-reperfusion (IR) injury. The IR-subjected mice exhibited a drastic increase in plasma citrullinated histone 3 (CitH3) and neutrophil elastase (NE) on day 1 (p < 0.05) while deoxyribonucleic acid (DNA) and myeloperoxidase (MPO) reached their peak levels on day 3. IR-subjected mice also showed a significant increase in peripheral neutrophils and decline in peripheral leukocytes, lymphocytes, and monocytes on day 1 and day 2 (p < 0.05). The ratios of neutrophil to lymphocyte, neutrophil to leukocyte, and lymphocyte to monocyte dramatically increased on day 1 (p < 0.05). Plasma NE, CitH3 and MPO were positively correlated with peripheral neutrophil and the ratio of neutrophil to lymphocyte, but inversely correlated with peripheral lymphocyte (p < 0.05). Our data suggest that there are time dependent changes in plasma NETosis biomarkers. Therefore, targeting these biomarkers before their peak may offer potential therapeutic options to reduce cerebral infarction and prevent functional deterioration after acute ischemic stroke.

Acute Brain Ischemia, Infarction and Hemorrhage in Subjects Dying with or Without Autopsy-Proven Acute Pneumonia

Stroke is one of the most serious complications of Covid-19 disease but it is still unclear whether stroke is more common with Covid-19 pneumonia as compared to non-Covid-19 pneumonia. We investigated the concurrence rate of autopsy-confirmed acute brain ischemia, acute brain infarction and acute brain hemorrhage with autopsy-proven acute non-Covid pneumonia in consecutive autopsies in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study of normal aging and neurodegenerative diseases. Of 691 subjects with a mean age of 83.4 years, acute pneumonia was histopathologically diagnosed in 343 (49.6%); the concurrence rates for histopathologically-confirmed acute ischemia, acute infarction or subacute infarction was 14% and did not differ between pneumonia and non-pneumonia groups while the rates of acute brain hemorrhage were 1.4% and 2.0% of those with or without acute pneumonia, respectively. In comparison, in reviews of Covid-19 publications, reported clinically-determined rates of acute brain infarction range from 0.5% to 20% while rates of acute brain hemorrhage range from 0.13% to 2%. In reviews of Covid-19 autopsy studies, concurrence rates for both acute brain infarction and acute brain hemorrhage average about 10%. Covid-19 pneumonia and non-Covid-19 pneumonia may have similar risks tor concurrent acute brain infarction and acute brain hemorrhage when pneumonia is severe enough to cause death. Additionally, acute brain ischemia, infarction or hemorrhage may not be more common in subjects dying of acute pneumonia than in subjects dying without acute pneumonia.

Clinical neuropsychological pathology profile of Moyamoya disease

The goal of this study is to discover and describe the clinical qualities of higher cortical functions in a young Moyamoya patient with acute brain ischemia. We assessed the recovery of higher cortical functions for the period from March 2019 to January 2020. This paper presents the individual patients medical history and the neuropsychological evaluation conducted during the patients rehabilitation in January 2020.

Perioperative acute internal carotid thrombosis after general surgery

Introduction: The average incidence of perioperative stroke during major non-cardiac surgery is less than 1%, suggesting that it is rarely a major problem for the vast majority of patients. Methods: In our paper we present a 46-year-old patient undergoing acute right hemicolectomy who developed right-sided hemiparesis in the perioperative setting. Immediate CTAg examination showed an ischemic stroke in the left hemisphere as a result of left internal carotid thrombosis. A surgical procedure to recanalize the left carotid artery was performed 14 hours from the onset of neurological symptomatology and the neurological deficit gradually recovered fully. Conclusion: Our case report supports studies showing that a thorough diagnostic assessment allows the selection of patients who may benefit from urgent revascularization of acute internal carotid occlusion during the phase of acute brain ischemia.

Features of the dynamics of inflammation and apoptosis markers in patients with different acute post-stroke period

The purpose of this was to study the dynamics of markers of inflammation and apoptosis in the serum of patients with ischemic stroke in the early post-stroke period. Materials and methods. The study involved 22 patients (mean age 60 ± 5.5 years) with different dynamics of neurological symptoms in the acute post-stroke period. Patients were examined twice: on the 1st and 10th day of observation. Quantitative assessment of the severity of neurological deficit using ESS and NIHSS scales was carried. Enzymatic activity of leukocyte elastase, functional activity of a1-proteinase inhibitor, level of autoantibodies to MBP (inflammatory markers), as well as the content of p53 and Bcl-2 proteins (markers of apoptosis) were determined in serum. The control group consisted of 35 somatically healthy people of the appropriate age and sex. Results. Identified the different features of the spectrum of the analyzed markers of inflammation and apoptosis in patients with positive and negative dynamics of neurological symptoms in the acute period of ischemic stroke assessed according to the ESS and NIHSS scales. The observed clinical and biological relationships reflect the features of the course of the early post-stroke period and can be considered as possible predictors of the development trajectory of acute brain ischemia.

Molecular control of protein synthesis, glucose metabolism, and apoptosis in the brain of hibernating thirteen-lined ground squirrels

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) are excellent models for studying acute brain ischemia because they show high resistance to reductions in blood flow and oxygen delivery without evidence of neurological damage. In this study, we analyzed the insulin signaling pathway and regulation of mitochondrial substrate oxidation in three regions of ground squirrel brain (forebrain, cerebellum, and brainstem), comparing summer, late torpor, and interbout arousal conditions. We found select decreases in phospho-Akt in the cerebellum during torpor compared with summer animals, as well as select increases in the forebrain during interbout arousal, suggesting that Akt may influence either metabolism or cytoprotective pathways. The phosphoprotein abundance of glycogen synthase kinase 3 beta (GSK3β) showed the most consistent trend across all three brain regions, with peak increases observed during deep torpor, suggesting a crucial role for this protein during hibernation. Furthermore, all three regions of the brain showed increased phospho-protein abundance of pyruvate dehydrogenase at serine 232 during both deep torpor and interbout arousal, and serine 300 during interbout arousal only, whereas other phosphorylation sites showed a region-specific expression pattern. Information collected from these studies sheds light on the molecular controls governing insulin signaling and fuel utilization in the brain of hibernating ground squirrels.

METHODS FOR SIMULATION OF ACUTE BRAIN ISCHEMIA: PATHOPHYSIOLOGICAL SUBSTANTIATION OF SELECTION AND IMPORTANCE FOR CLINICAL PRACTICE

Одним из основных требований к разработке экспериментальных моделей цереброваскулярных заболеваний является их максимальная приближенность к реальной клинической практике. В работе систематизированы данные по основным методам моделирования острой ишемии головного мозга (ОИГМ), представлена их классификация, анализируются данные о преимуществах и недостатках той или иной модели. Обсуждаются результаты экспериментальных исследований по изучению патогенеза ОИГМ с использованием различных моделей (полной и неполной глобальной, локальной и мультифокальной ишемии) и способов их реализации (перевязка артерий, клипирование, коагуляция, эмболизация и др.). Особое внимание уделяется «стабильности» последствий острого нарушения мозгового кровообращения: необратимых ишемических повреждений головного мозга или обратимых с реперфузией заданной продолжительности. Отмечается, что важное значение в этих исследованиях должно принадлежать современным методам прижизненной визуализации очагов острого ишемического повреждения, что позволяет оценивать динамику патологического процесса. Предлагаемый метод отвечает требованиям гуманного обращения с животными. Подчеркивается, что выбор релевантной модели ОИГМ определяется задачами предстоящего исследования и технологическими ресурсами научной лаборатории. Development of experimental models for acute forms of cerebrovascular diseases is essential for implementation of methods for their prevention and treatment. One of the principal requirements to such models is their maximum approximation to actual clinical practice. This review systematized major models of acute cerebral ischemia (ACI), their classification, and presented information about their advantages and shortcomings. Also, the review presented results of experimental studies on pathophysiological mechanisms of different types of modeled ACI (complete and incomplete global, local, and multifocal ischemia) and methods for creating these models (arterial ligation, clipping, coagulation, embolization, etc.). Particular attention was paid to “stability” of the consequences of acutely impaired cerebral circulation - an irreversible ischemic brain injury or a reversible injury with reperfusion of a given duration. The authors emphasized that in such studies, a special significance should be given to intravital imaging of acute ischemic damage foci using modern methods, which allow assessing the dynamics of the pathological process and meet the requirements to humane treatment of animals. The choice of a relevant ACI model is determined by objectives of the planned study and the technological resources available at the research laboratory.

An exploratory investigation of brain collateral circulation plasticity after cerebral ischemia in two experimental C57BL/6 mouse models

Brain collateral circulation is an essential compensatory mechanism in response to acute brain ischemia. To study the temporal evolution of brain macro and microcollateral recruitment and their reciprocal interactions in response to different ischemic conditions, we applied a combination of complementary techniques (T2-weighted magnetic resonance imaging [MRI], time of flight [TOF] angiography [MRA], cerebral blood flow [CBF] imaging and histology) in two different mouse models. Hypoperfusion was either induced by permanent bilateral common carotid artery stenosis (BCCAS) or 60-min transient unilateral middle cerebral artery occlusion (MCAO). In both models, collateralization is a very dynamic phenomenon with a global effect affecting both hemispheres. Patency of ipsilateral posterior communicating artery (PcomA) represents the main variable survival mechanism and the main determinant of stroke lesion volume and recovery in MCAO, whereas the promptness of external carotid artery retrograde flow recruitment together with PcomA patency, critically influence survival, brain ischemic lesion volume and retinopathy in BCCAS mice. Finally, different ischemic gradients shape microcollateral density and size.