Glutamine synthetase expression in the brain during experimental acute liver failure (immunohistochemical study)

The aim of the study was to determine the immunohistochemical level of glutamine synthetase (GS) expression in different brain regions in the conditions of experimental acute liver failure in rats. Materials and methods. The study was conducted in Wistar rats: 5 sham (control) animals and 10 rats with acetaminophen induced liver failure model (AILF). The immunohistochemical study of GS expression in the sensorimotor cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen was carried out in the period of 12-24 h after acetaminophen treatment. Results. Beginning from the 6th hour after acetaminophen treatment all AILF-animals showed the progressive increase in clinical signs of acute brain disfunction finished in 6 rats by comatose state up to 24 h - they constituted subgroup AILF-B, “non-survived”. 4 animals survived until the 24 h - subgroup AILF-A, “survived”. In the AILF-B group, starting from 16 to 24 hours after treatment, a significant (relative to control) regionally-specific dynamic increase in the level of GS expression was observed in the brain: in the cortex – by 307.33 %, in the thalamus – by 249.47%, in the hippocampus – by 245.53%, in the subcortical white matter – by 126.08%, from 12th hour – in the caudate nucleus/putamen, by 191.66 %; with the most substantive elevation of GS expression in the cortex: by 4.07 times. Conclusion. Starting from the 16th hours after the acetaminophen treatment (from the 12th h in the caudate nucleus/putamen region) and up to 24 h, it is observed reliable compared to control dynamic increase in GS protein expression in the cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen of the rat brain with the most significant elevation in the cortex among other regions. The heterogeneity in the degree of GS expression rising in different brain regions potentially may indicate regions more permeable for ammonia and/or other systemic toxic factors as well as heterogeneous sensitivity of brain regions to deleterious agents in conditions of AILF. Subsequently, revealed diversity in the GS expression reflects the specificity of reactive response of local astroglia in the condition of AILF-encephalopathy during specific time-period. The dynamic increase in the GS expression associated with impairment of animal state, indicates involvement of increased GS levels in the mechanisms of experimental acute hepatic encephalopathy.

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Immunohistochemical analysis of GFAP expression in the experimental sepsis-associated encephalopathy

Pathologia ◽

10.14739/2310-1237.2021.3.240033 ◽

2021 ◽

Vol 18 (3) ◽

pp. 295-302

Author(s):

T. V. Shulyatnikova ◽

V. O. Tumaskyi

Keyword(s):

White Matter ◽

Caudate Nucleus ◽

Critical Role ◽

Brain Regions ◽

Subcortical White Matter ◽

Control Group ◽

Experimental Sepsis ◽

Respiratory Impairment ◽

Gfap Expression ◽

The Brain

Pathophysiology of sepsis-associated encephalopathy (SAE) is linked to blood-brain barrier breakdown, neuroinflammation and neurotransmitter imbalance in the brain. Astroglia, the most abundant cell population within the brain, plays the critical role in control of all kinds of homeostatic processes, thereby regulating the adaptive reactions of the brain to various challenges. Astroglia are highly heterogenous across the brain regions, therefore, damaging factors stimulate heterogenous astroglial reactivity and response in different brain regions. The aim of this study was determining immunohistochemical features of GFAP expression in various brain regions in the model of rodent experimental sepsis. Materials and methods. The experiment was performed in Wistar rats: control group of 5 sham-operated rats and the main group of 20 rats subjected to cecum ligation and puncture (CLP) procedure. The immunohistochemical study of GFAP expression in the sensorimotor cortex, subcortical white matter, hippocampal, thalamic and caudate nucleus/putamen regions was performed from 20 to 48 hours of the postoperative period. Results. Starting from the 12th hour after CLP, animals began display progressive increase in signs of periorbital exudation, piloerection, fever-/hypothermia, diarrhea, social isolation, lethargy, and respiratory impairment. In the period of 20–38 hours, 9 animals showed expressed previously listed symptoms and were euthanized (CLP-B – lethal group), 11 rats survived until 48 hours of the experiment (CLP-A – survived group). In the lethal group, starting from 20 to 38 hours after the CLP procedure, a significant (relative to control) regionally-specific dynamic increase in the level of GFAP expression was observed in the brain: in the cortex – by 465 %, in the subcortical white matter – by 198 %, in the hippocampus – by 250 %, from the 23rd hour – in the caudate nucleus/putamen by 18 %. In the thalamus, no significant changes in the level of GFAP expression were observed. In the cortex and hippocampus of survived animals, 48 h after CLP, higher values of GFAP expression were observed comparing to the group of non-survived animals. Conclusions. Under conditions of the experimental SAE, an early dynamic increase in the astroglial reactivity was observed in the cortex, hippocampus, white matter, and caudate nucleus/putamen of the brain with the most significant increase of indicators in the cortex and hippocampus, which potentially indicates relatively more vulnerable areas of the brain to damaging factors, as well as places of the most active intercellular interaction in the condition of systemic inflammation. Higher values of GFAP expression in the cortex and hippocampus of survived animals at 48 hours of the experiment, compared with indicators of non-survived group, indicate increased astroglial reactivity in these brain regions at the noted time period, accompanied by relatively more favorable clinical course of the disease.

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Wilson Disease-Induced Acute Liver Failure (NWI = 13) Salvaged without Liver Transplant by Plasmapheresis

Journal of Child Science ◽

10.1055/s-0041-1731079 ◽

2021 ◽

Vol 11 (01) ◽

pp. e145-e147

Author(s):

Nida Mirza ◽

Ravi Bharadwaj ◽

Smita Malhotra ◽

Anupam Sibal

Keyword(s):

Liver Transplantation ◽

Liver Failure ◽

Acute Liver Failure ◽

Wilson Disease ◽

Prognostic Score ◽

Prognostic Index ◽

Kidney Injury ◽

Copper Metabolism ◽

Life Saving ◽

The Brain

AbstractWilson disease (WD) is a disorder of copper metabolism resulting in accumulation of copper in vital organs of the human body, predominantly in the liver and the brain. Acute liver failure in WD has a bad prognosis, especially with a score ≥11 in the revised WD prognostic index; emergency liver transplantation is considered the only life-saving option in this scenario. Here, we reported a girl patient with WD-induced liver failure and poor prognostic score who was rescued by plasmapheresis. She also manifested severe Coombs negative hemolytic anemia and acute kidney injury. This case report highlights the utility of an adjunctive modality besides liver transplantation for the management of fulminant liver failure caused by WD.

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COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis

BMC Infectious Diseases ◽

10.1186/s12879-021-06605-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jana Ihlow ◽

Alexander Seelhoff ◽

Victor M. Corman ◽

Achim D. Gruber ◽

Simon Dökel ◽

...

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Liver Damage ◽

Cathepsin L ◽

Fatal Case ◽

Clinical Signs ◽

Angiotensin Converting Enzyme 2 ◽

Severe Liver Damage ◽

Severe Jaundice ◽

Transmembrane Serine Protease

Abstract Background The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. Case presentation Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2). Conclusion Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.

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S-Adenosylmethionine Deficiency and Brain Accumulation of S-Adenosylhomocysteine in Thioacetamide-Induced Acute Liver Failure

Nutrients ◽

10.3390/nu12072135 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2135

Author(s):

Anna Maria Czarnecka ◽

Wojciech Hilgier ◽

Magdalena Zielińska

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Redox Homeostasis ◽

Cerebral Function ◽

Total Glutathione ◽

Cellular Redox ◽

Therapeutic Value ◽

Transsulfuration Pathway ◽

Subsequent Hydrolysis ◽

The Brain

Background: Acute liver failure (ALF) impairs cerebral function and induces hepatic encephalopathy (HE) due to the accumulation of neurotoxic and neuroactive substances in the brain. Cerebral oxidative stress (OS), under control of the glutathione-based defense system, contributes to the HE pathogenesis. Glutathione synthesis is regulated by cysteine synthesized from homocysteine via the transsulfuration pathway present in the brain. The transsulfuration-transmethylation interdependence is controlled by a methyl group donor, S-adenosylmethionine (AdoMet) conversion to S-adenosylhomocysteine (AdoHcy), whose removal by subsequent hydrolysis to homocysteine counteract AdoHcy accumulation-induced OS and excitotoxicity. Methods: Rats received three consecutive intraperitoneal injections of thioacetamide (TAA) at 24 h intervals. We measured AdoMet and AdoHcy concentrations by HPLC-FD, glutathione (GSH/GSSG) ratio (Quantification kit). Results: AdoMet/AdoHcy ratio was reduced in the brain but not in the liver. The total glutathione level and GSH/GSSG ratio, decreased in TAA rats, were restored by AdoMet treatment. Conclusion: Data indicate that disturbance of redox homeostasis caused by AdoHcy in the TAA rat brain may represent a deleterious mechanism of brain damage in HE. The correction of the GSH/GSSG ratio following AdoMet administration indicates its therapeutic value in maintaining cellular redox potential in the cerebral cortex of ALF rats.

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Quantitative multivoxel 1H MR spectroscopy of the brain in children with acute liver failure

European Radiology ◽

10.1007/s00330-008-1049-z ◽

2008 ◽

Vol 18 (11) ◽

pp. 2601-2609 ◽

Cited By ~ 14

Author(s):

Paul E. Sijens ◽

Heyder Alkefaji ◽

Roelineke J. Lunsing ◽

Francjan J. van Spronsen ◽

Linda C. Meiners ◽

...

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Mr Spectroscopy ◽

1H Mr Spectroscopy ◽

The Brain

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Subchronic treatment with acai frozen pulp prevents the brain oxidative damage in rats with acute liver failure

Metabolic Brain Disease ◽

10.1007/s11011-016-9873-3 ◽

2016 ◽

Vol 31 (6) ◽

pp. 1427-1434 ◽

Cited By ~ 5

Author(s):

Fernanda de Souza Machado ◽

Jonnsin Kuo ◽

Mariane Farias Wohlenberg ◽

Marina da Rocha Frusciante ◽

Márcia Freitas ◽

...

Keyword(s):

Oxidative Damage ◽

Liver Failure ◽

Acute Liver Failure ◽

Subchronic Treatment ◽

The Brain

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NMR study of 13C-glucose and 13C-acetate metabolism in the brain of rats with acute liver failure

Journal of Neurochemistry ◽

10.1046/j.1471-4159.81.s1.3_20.x ◽

2008 ◽

Vol 81 ◽

pp. 9-13

Author(s):

C. Zwingmann ◽

N. Chatauret ◽

D. Leibfritz ◽

R. F. Butterworth

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Acetate Metabolism ◽

Nmr Study ◽

The Brain

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The Na–K–Cl cotransporter in the brain edema of acute liver failure

Journal of Hepatology ◽

10.1016/j.jhep.2010.06.041 ◽

2011 ◽

Vol 54 (2) ◽

pp. 272-278 ◽

Cited By ~ 31

Author(s):

Arumugam R. Jayakumar ◽

Vanessa Valdes ◽

Michael D. Norenberg

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Brain Edema ◽

The Brain

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Microsurgical anatomy of the central core of the brain

Journal of Neurosurgery ◽

10.3171/2017.5.jns162897 ◽

2018 ◽

Vol 129 (3) ◽

pp. 752-769 ◽

Cited By ~ 13

Author(s):

Eduardo Carvalhal Ribas ◽

Kaan Yağmurlu ◽

Evandro de Oliveira ◽

Guilherme Carvalhal Ribas ◽

Albert Rhoton

Keyword(s):

White Matter ◽

Caudate Nucleus ◽

Internal Capsule ◽

Central Core ◽

Surgical Approaches ◽

Microsurgical Anatomy ◽

Functional Importance ◽

Posterior Portion ◽

External Capsule ◽

The Brain

OBJECTIVEThe purpose of this study was to describe in detail the cortical and subcortical anatomy of the central core of the brain, defining its limits, with particular attention to the topography and relationships of the thalamus, basal ganglia, and related white matter pathways and vessels.METHODSThe authors studied 19 cerebral hemispheres. The vascular systems of all of the specimens were injected with colored silicone, and the specimens were then frozen for at least 1 month to facilitate identification of individual fiber tracts. The dissections were performed in a stepwise manner, locating each gray matter nucleus and white matter pathway at different depths inside the central core. The course of fiber pathways was also noted in relation to the insular limiting sulci.RESULTSThe insular surface is the most superficial aspect of the central core and is divided by a central sulcus into an anterior portion, usually containing 3 short gyri, and a posterior portion, with 2 long gyri. It is bounded by the anterior limiting sulcus, the superior limiting sulcus, and the inferior limiting sulcus. The extreme capsule is directly underneath the insular surface and is composed of short association fibers that extend toward all the opercula. The claustrum lies deep to the extreme capsule, and the external capsule is found medial to it. Three fiber pathways contribute to form both the extreme and external capsules, and they lie in a sequential anteroposterior disposition: the uncinate fascicle, the inferior fronto-occipital fascicle, and claustrocortical fibers. The putamen and the globus pallidus are between the external capsule, laterally, and the internal capsule, medially. The internal capsule is present medial to almost all insular limiting sulci and most of the insular surface, but not to their most anteroinferior portions. This anteroinferior portion of the central core has a more complex anatomy and is distinguished in this paper as the “anterior perforated substance region.” The caudate nucleus and thalamus lie medial to the internal capsule, as the most medial structures of the central core. While the anterior half of the central core is related to the head of the caudate nucleus, the posterior half is related to the thalamus, and hence to each associated portion of the internal capsule between these structures and the insular surface. The central core stands on top of the brainstem. The brainstem and central core are connected by several white matter pathways and are not separated from each other by any natural division. The authors propose a subdivision of the central core into quadrants and describe each in detail. The functional importance of each structure is highlighted, and surgical approaches are suggested for each quadrant of the central core.CONCLUSIONSAs a general rule, the internal capsule and its vascularization should be seen as a parasagittal barrier with great functional importance. This is of particular importance in choosing surgical approaches within this region.

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Halicephalobus gingivalis (H.deletrix) in the brain of a horse

Ciência Rural ◽

10.1590/s0103-84782007000400047 ◽

2007 ◽

Vol 37 (4) ◽

pp. 1185-1187 ◽

Cited By ~ 7

Author(s):

Rosemeri de Oliveira Vasconcelos ◽

Karen Regina Lemos ◽

Julieta Rodini Engracia de Moraes ◽

Vívian Palmeira Borges

Keyword(s):

White Matter ◽

Histological Examination ◽

Inflammatory Infiltrate ◽

Clinical Signs ◽

Nematode Infection ◽

Etiological Agent ◽

Axonal Spheroids ◽

The Brain ◽

Halicephalobus Gingivalis

A 10-year-old Mangalarga gelding with rhabditiform nematode infection in the brain is described. Clinical signs were limited to circling and right side paralysis. Histological examination of the brain revealed marked gliosis and discreet edema. The perivascular mononuclear inflammatory infiltrate was composed of few layers of lymphocytes, plasmocytes and macrophages and rare eosinophils. The presence of rhabditiform nematodes was associated with the infiltrate. Areas of malacia associated with the parasites and parasite tracks with axonal spheroids were also seen close to the vessels and to the etiological agent and were more evident in the white matter. In the meninges there was moderate inflammatory infiltrate associated with perivascular parasites. The identification of the nematode was based on the histological examination of the cerebral fragments.

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