Background: Spontaneous intracerebral hemorrhage (ICH) is one of the leading causes of mortality in intensive care units. The role of systemic hyperintense inflammation (SHI) in the pathogenesis of critical complications of ICH remains a poorly understood problem. There is a specific variant of severe ICH associated with increased intracranial pressure and occlusion of intracranial vessels, defined as ineffective cerebral blood flow (IECBF). Methods: To evaluate the role of SHI in the pathogenesis of severe (comatose) ICH in a dynamic comparison of patients with IECBF (n-26) and without IECBF (n-52). The SHI integral score criterion (SI scale) was used, including certain values of plasma concentrations of IL-6, IL-8, IL-10; TNF-α, PCT, cortisol, myoglobin, troponin I, D-dimer, and, additionally, SOFA scale values. Blood levels of ACTH and neuron-specific enolase (NSE) were also assessed. Results: Twenty-eight-day mortality in severe ICH reached 84.6% (without IECBF) and 96.2% (with IECBF). Clear signs of SHI were detected in 61.5%/87.8% (without IECBF) and 0.0%/8.7% (with IECBF) within 1–3/5–8 days from the onset of ICH manifestation. The lower probability of developing SHI in the IECBF group was associated with low blood NSE concentrations. Conclusions: The development of SHI in ICH is pathogenetically related to the permeability of the blood–brain barrier for tissue breakdown products and other neuroinflammatory factors.

Черепно-мозговая травма и нейровоспаление: обзор основных биомаркеров

Acetaminophen is one of the most toxic drugs that can cause liver damage. At the same time, acetaminophen-induced liver failure is closely associated with the development of systemic inflammatory response syndrome. However, there is no drug aimed at suppressing the systemic inflammatory response. That is, this issue needs to be studied experimentally, but a model of systemic inflammation during acetaminophen overdose has not yet been obtained. Therefore, it was decided to develop an experimental model of systemic inflammation during acetaminophen overdose. The purpose of this study was to experimentally substantiate the semi-lethal dose for acetaminophen overdose in C57Bl/6 mice and to evaluate the readings of blood tests after administration of the drug. To determine the semi-lethal dose, male C57Bl/6 mice were intraperitoneally injected with “Ifimol” (Unique Pharmaceutical Laboratories, India) or acetaminophen solution (Sigma-Aldrich, USA) with a concentration of 14 mg/ml in different doses. When introducing “Ifimol”, it was not possible to achieve a semi-lethal dose. When administering a solution of acetaminophen, 50% mortality was recorded at a dose of 600 mg/kg body weight. After establishing a semi-lethal dose, the experimental group was administered an acetaminophen solution (Sigma-Aldrich, USA) with a concentration of 14 mg/ml at a dose of 600 mg/kg. The control group was injected with saline in an equivalent volume. On the second day, liver and peripheral blood samples were taken. Subsequently, hematological and biochemical blood tests and histological analysis were performed. Histological examination revealed centrilobular necrosis and disorganization of the liver structure. According to the biochemical blood test, the activity of aspartate aminotransferase, alanine aminotransferase, creatinine concentration, and the de Ritis coefficient differed statistically significantly (p 0.05) in the experimental group compared to the control group. Among the hematological blood test parameters, there were statistically significant differences in the number of leukocytes, platelets, as well as the absolute and relative content of granulocytes and lymphocytes. Thus, 48 hours after administration of a semi-lethal dose of acetaminophen, there were signs of damage to internal organs (liver, kidneys) and changes in immune system parameters, which are similar to components of systemic inflammation in humans.

Paracetamol is one of the five most common drugs causing fatal hepatotoxicity. The mouse model of paracetamol hepatotoxicity adequately reflects the mechanism of drug poisoning in humans. However, there are many controversies associated with understanding the pathogenetic mechanisms of process.   Aim of the study was to reveal the signs of systemic damage of various organs on the basis of estimation of haematological and biochemical indices of peripheral blood of experimental animals after administration of a half-year dose of paracetamol.   Material and methods. Male C57Bl/6 mice aged 10 weeks were given a single intraperitoneal injection of a paracetamol solution at a concentration of 14 mg/ml at a dose of 600 mg/kg body weight or saline in an equivalent volume, after 6, 12, 24 and 48 hours, blood was collected and haematological and biochemical analysis were performed.   Results and discussion. Paracetamol administration causes in mice an increase in alanine and aspartate aminotransferase activity, decrease in total protein, albumin, globulin content. There is an increase in the urea and creatinine level. Transient monocytopenia, lympho- and thrombocytopenia, granulocytosis are observed in peripheral blood.   Conclusions. After administration of paracetamol at a dose of 600 mg/kg body weight, signs of liver (change of alanine and aspartate aminotransferase activity, total protein and urea content) and kidney (creatinine level) dysfunction were detected in mice. In peripheral blood, the classic picture of inflammatory response is determined (lymphopenia and granulocytosis) with signs of impaired haemostasis in the form of thrombocytopenia. No generalized changes affecting all organs were detected, which determines the need to use more sensitive and specific methods to detect signs of systemic inflammation.

Acetaminophen (paracetamol) is one of the most common analgesic and antipyretic agents. Therefore, the overdosage with this drug are often observed, being associated with acute hepatotoxicity and systemic inflammation, worsening the clinical prognosis. In this case, systemic inflammation is characterised by systemic activation of immune system. However, the contribution of different types of immune cells to pathogenesis of acetaminophen poisoning has not been sufficiently studied thus determining the purpose of this work. The aim of this study was to evaluate changes in the number of cells expressing CD3+, CD20+, CD45+ in organs of C57Bl/6 mice during acute acetaminophen poisoning. The study was performed with sexually mature male C57Bl/6 mice. The mice were divided into 2 groups of 7 mice in each group. The experimental group included animals treated with acetaminophen solution (Sigma-Aldrich, USA) at a dose of 600 mg/kg at (14 mg/mL). An equivalent volume of physiological solution was administered to the control group. The animals were taken out of the experiment after 24 hours, and internal organs were removed. Primary rabbit antibodies from Sigma-Aldrich (C7930), Thermo Fisher Scientific (PA5-16701), Abcam (ab281586) were used for immunohistochemical study for CD3+, CD20+, CD45+ cells. Secondary antibodies were purchased from Thermo Fisher Scientific (31820). When assessing the content of CD20+ cells in organ tissues of C57Bl/6 mice, only single cells were observed in the field of view. Statistically significant differences were not revealed by Mann–Whitney U test thus suggesting absence of B cell contribution to the pathogenesis of acetaminophen poisoning in the first 24 hours. A statistically significant decrease in the number of CD3+ cells in heart tissue was determined. 24 hours after the toxicant administration, an increased number of CD45+ expressing immune cells was noted in liver, mainly, as segmented neutrophils. Hence, we did not find any significant changes in cell numbers of CD3+ and CD20+ expressing cells in the studied tissues by 24 hours after acute acetaminophen poisoning in experimental animals. At the same time, there is an increased content of immune cells in the liver tissue, mainly due to neutrophils.

The steady increase in the incidence of heart and pancreatic diseases, as well as the lack of information on the effect of paracetamol on the structure of these organs, necessitate the study of morphometric changes in poisoning with this drug, especially in the context of oral use of this drug and the growing number of cases of paracetamol overdose. Paracetamol, often used as an analgesic and antipyretic, has a narrow therapeutic index, which makes its toxicity a particularly relevant topic for clinical and pathophysiological research. The purpose of the study. To analyze morphometric changes in the pancreas and myocardium of C57Bl/6 mice with acute paracetamol poisoning. Materials and methods. The experiment was conducted on male C57Bl/6 mice (n=21), divided into intact, control, and experimental groups. Paracetamol (600 mg/kg) was administered intraperitoneally to the experimental group, and saline solution was administered to the control group. After 6 hours, the pancreas and heart were removed for histological and morphometric studies. Conclusions. In acute paracetamol poisoning in C57Bl/6 mice in the early stages (after 6 hours) There are no morphometric and histological signs of dystrophic-necrotic changes in the heart or acute pancreatitis in the pancreas.