ABSTRACT
The paper describes white matter lesions that differ from periventricular leukomalacia (PVL), such as diffuse leukomalacia (DL) and telencephalic gliosis (TG). There are three types of cerebral leukomalacias: PVL, DL, and subcortical leukomalacia. The morphological differences between PVL and DL are considered. The diffuse form of PVL is described. It is pointed out that colliquation PVL foci frequently occur in infants with birth weight less than 1500 g. There are data on the morphology of TG in which generalized and occasionally large-focal astrogliosis develops in the cerebral hemispheric white matter. It is suggested that it is inexpedient to identify the focal and diffuse components of PVL. The immunihistochemical findings led to the conclusion that PVL, DL, and TG did not result from the direct effects of pathogens of inherited infections on brain tissue.
Subject(s)
Cerebral Cortex/physiopathology , Leukoencephalopathies/physiopathology , Leukomalacia, Periventricular/physiopathology , Autopsy , Gliosis/pathology , Humans , Infant , Infant, Newborn , Leukomalacia, Periventricular/classification , Leukomalacia, Periventricular/diagnosis , Nervous System Diseases/physiopathologyABSTRACT
INTRODUCTION: Influenza A virus infection can lead to endothelial dysfunction (ED), including apoptosis of endothelial cells and modulation of endothelial factor activities. Affected biochemical factors may include those playing important roles in vascular homeostasis. However, the effect of this pathogen on the expression pattern of key endothelial factors is still unknown.The aim of this work was to study the expression of endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1, serpin E1) in the EA.hy926 endothelial cells. RESEARCH OBJECTIVES: to assess expression of eNOS and PAI-1 in endothelial cells infected with influenza virus A(H1N1)pdm09, and to identify homologous fragments in structure of viral proteins and endothelial factors. MATERIAL AND METHODS: Cells were infected with influenza virus A/St. Petersburg/48/16 (H1N1)pdm09 and analyzed in dynamics in 6, 12, 18, 24, 48, and 72 hrs post infection (hpi). Detection of endothelial factors expression levels was performed by immunocytochemical method (ICC) using antibodies for eNOS and PAI-1 while quantitative assessment of expression levels was carried out by program Nis-Elements F3.2 («Nikon¼, Japan). The search for homologous sequences between viral proteins and eNOS and PAI-1 was performed by computer comparison. Sequences were analyzed as fragments 12 amino acid residues (aar) in length. RESULTS AND DISCUSSION: eNOS expression in infected cells had decreased to 7.9% by 6 hpi (control was taken as 100%) to 3.3% at 72 hpi. PAI-1 expression varied significantly over the course of the experiment: by 6 hpi it had decreased to 49.6%, and to 43.2% by 12 hpi. Later PAI-1 levels were: 116.3% (18 hpi); 18.9% (24 hpi); 23.5% (48 hpi), and 35% (72 hpi). CONCLUSION: These results indicate that influenza A infection of endothelial cells causes a significant decrease in eNOS expression, while modulating PAI-1 one. The described phenomenon can be used in the further development of directions of pathogenetic therapy of vascular complications of infection caused by this pathogen.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Nitric Oxide Synthase Type III/metabolism , Plasminogen Activator Inhibitor 1/metabolism , Endothelial Cells , Humans , Plasminogen Activator Inhibitor 1/genetics , Viral ProteinsABSTRACT
It has now been established that blood vessels are target for influenza, but the mechanism by which the influenza virus affects the cardiovascular system is unknown. The aim - adaptation of influenza virus A/St. Petersburg/48/16 H1N1(pdm09) to mature Wistar rats, as these animals are the main experimental model for studying the pathology of the cardiovascular system. MATERIAL AND METHODS: Passage of influenza A virus (IAV) in embryonated chicken eggs, intranasal inoculation of rats with virus-containing material s, production of pulmonary homogenate, determination of IAV titer in embryonated chicken eggs, detection of histological changes in lung and pulmonary vessels. RESULTS: The article presents the results of the adaptation of influenza virus A/St. Petersburg/48/16 H1N1(pdm09) to mature Wistar rats. The infectious titer of the virus in the homogenates of infected rats lungs at the last stage of adaptation was 7.0 lg EID50/ml. Histological studies revealed pronounced changes in the respiratory tract (spasm of bronchioles, submucosal edema, desquamation of ciliated epithelium of bronchioles) and pulmonary vessels (spasm, desquamation and swelling of endotheliocytes, dissociation and swelling of the elastic membrane and media). In order to identify IAV in blood vessels and lung tissues, an immunohistochemical study was performed using monoclonal antibodies to NP antigen of IAV. CONCLUSION: The data obtained allow us to conclude that the strain of influenza virus A/St. Petersburg/48/16 H1N1(pdm09) was adapted to mature Wistar rats maintaining virulent properties. The infectious titer of the virus at the last stage of adaptation was 7.0 lg EID50/ml. IAV identification is confirmed by immunohistochemical examination.