scholarly journals Immunohistochemical analysis of microglial changes in the experimental acute hepatic encephalopathy

Pathologia ◽  
2021 ◽  
Vol 18 (1) ◽  
pp. 33-38
Author(s):  
T. V. Shulyatnikova
Keyword(s):  
Hepatic Encephalopathy ◽  
White Matter ◽  
Liver Failure ◽  
Rat Brain ◽  
Subcortical White Matter ◽  
Time Dependent ◽  
Brain Cells ◽  
Caudate Putamen ◽  
Reactive Changes ◽  
The Brain

Hepatic encephalopathy (HE) is a syndrome of impaired brain function in patients with advanced liver failure and it manifests in form of psychometric tests alterations up to decreased consciousness and coma. The current knowledge about HE mainly focused on the theory of ammonia neurotoxicity and neuroinflammation. Microglia being resident innate immune cells of the brain when activated are responsible for the neuroinflammatory reactions. The aim – immunohistochemical study of the microglial changes in different rat brain regions in conditions of experimental acute HE (AHE). Materials and methods. We used acetaminophen induced liver failure model in Wistar rats. Four from 10 animals that survived up to 24 h after acetaminophen injection constituted “compensated group”; 6 animals which died within 24 h – “decompensated group”. Microglial reactive changes were analysed by the evaluation of the relative area (S rel., %) of CD68+ expression in the brain cells not associated with meninges and vessels, as well as the changing in shape and number of these cells. Results. Acetaminophen-induced AHE in rats was characterized by the regional- and time-dependent dynamic increase in CD68 expression level in the rat brain in form of significant (relatively to control) increase of CD68+ S rel. in brain cells and the number of such cells. The medians of CD68+ S rel. and their numbers in significantly changed regions of non-survived rats were, respectively: subcortical white matter – 0.24 (0.20; 0.26) and 11.00 (8.00; 13.00); thalamus – 0.13 (0.90; 0.18) and 6.00 (3.00; 7.00); caudate/putamen – 0.13 (0.12; 0.18) and 7.00 (4.00; 11.00) – all indicators were statistically significant compared to control. In the survived animals, indicators were, respectively: subcortical white matter – 0.24 (0.16; 0,26) and 10.00 (8.00; 12.00); caudate/putamen – 0.12 (0.10; 0.15) and 6.00 (4.00; 10.00) – the differences were significant compared to control. Conclusions. The highest and significant indicators were revealed at 24 h (compared to earlier time points) of the experiment in the white matter, thalamus and caudate/putamen. This fact reflects time-dependent dynamic boosting of reactive changes in microglia and presumably may indicate the regions of the most active neuroinflammatory response within the brain parenchyma in the conditions of AHE. The appearing of a small percentage of cells with amoeboid transformation among CD68+-cells may mean partial functional insufficiency of such cells due to probable suppressive impact of ammonia or other influencing factors, as well as insignificance of the material that needs to be phagocytosed under established conditions.

scholarly journals Regional-specific activation of phagocytosis in the rat brain in the conditions of sepsis-associated encephalopathy

2021 ◽  
Vol 23 (1) ◽  
pp. 111-119
Author(s):  
T. V. Shulyatnikova ◽  
V. O. Shavrin
Keyword(s):  
White Matter ◽  
Rat Brain ◽  
Phagocytic Activity ◽  
Surrounding Tissue ◽  
Experimental Sepsis ◽  
Special Role ◽  
Caudate Putamen ◽  
Neuroinflammatory Response ◽  
Brain White Matter ◽  
The Brain

In the condition of sepsis-associated encephalopathy (SAE), the brain neuroinflammatory response is considered as one of the most critical mechanisms of tissue damage and impaired cerebral homeostasis. The main cell population of the brain responsible for the immune surveillance is microglia, and its phagocytic activity is a fundamental function providing both homeostatic and damaging properties. The aim of this study was to determine the immunohistochemical and ultrastructural specificity of the phagocytosis activation in different rat brain regions in the conditions of experimental sepsis. Materials and methods. The study was conducted in Wistar rats: 5 sham-operated animals and 20 rats with cecum ligation and puncture (CLP). The immunohistochemical study of CD68 expression in the cortex, white matter, hippocampus, thalamus, caudate/putamen was carried out in the period of 20–48 h postoperatively. The cerebral cortex was examined using transmission electron microscopy. Results. Beginning from the 20th h after CLP, there was a significant dynamic increase in the values of the relative area of CD68 expression, the number of immunopositive cells, as well as the percentage of immunopositive cells with amoeboid morphology in all animals of the CLP group, with a predominance of the indicators in the lethal group of rats. The highest levels of phagocytic activity were noted in the white matter and caudate/putamen in both the survived and non-survived animals. Ultrastructurally, the microgliocytes of the lethal group were characterized by signs of actively phagocytic cells and extensive glial-neuronal interaction; phagocytosing microglia in the survived animals showed an active involvement in the processes of necrotic debris elimination into the vasculature. Conclusions. In the conditions of SAE, there is the early and dynamic increase in phagocytosis activation with the predominant localization in the brain white matter and caudate/putamen, which could conceivably indicate a special role of these brain areas in the mechanisms of neuroinflammatory response in the conditions of systemic inflammation. In the brain of non-survived animals, the phagocytosis indices are higher than in the group of survivors, which most likely indicates a natural response of microglia to more pronounced destructive processes, but it does not preclude a concurrent neurotoxic activity of CD68-positive cells on the surrounding tissue elements.

What Has Direct Cortical and Subcortical Electrostimulation Taught Us about Neurolinguistics?

2019 ◽  
pp. 185-211
Author(s):  
Hugues Duffau
Keyword(s):  
White Matter ◽  
Large Scale ◽  
Functional Neuroimaging ◽  
Great Accuracy ◽  
Subcortical White Matter ◽  
Cerebral Lesions ◽  
Physiological Basis ◽  
Postoperative Mri ◽  
The Brain

Investigating the neural and physiological basis of language is one of the most important challenges in neurosciences. Direct electrical stimulation (DES), usually performed in awake patients during surgery for cerebral lesions, is a reliable tool for detecting both cortical and subcortical (white matter and deep grey nuclei) regions crucial for cognitive functions, especially language. DES transiently interacts locally with a small cortical or axonal site, but also nonlocally, as the focal perturbation will disrupt the entire subnetwork sustaining a given function. Thus, in contrast to functional neuroimaging, DES represents a unique opportunity to identify with great accuracy and reproducibility, in vivo in humans, the structures that are actually indispensable to the function, by inducing a transient virtual lesion based on the inhibition of a subcircuit lasting a few seconds. Currently, this is the sole technique that is able to directly investigate the functional role of white matter tracts in humans. Thus, combining transient disturbances elicited by DES with the anatomical data provided by pre- and postoperative MRI enables to achieve reliable anatomo-functional correlations, supporting a network organization of the brain, and leading to the reappraisal of models of language representation. Finally, combining serial peri-operative functional neuroimaging and online intraoperative DES allows the study of mechanisms underlying neuroplasticity. This chapter critically reviews the basic principles of DES, its advantages and limitations, and what DES can reveal about the neural foundations of language, that is, the large-scale distribution of language areas in the brain, their connectivity, and their ability to reorganize.

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

2021 ◽  
Vol 11 (10) ◽  
pp. 342-356
Author(s):  
T. Shulyatnikova ◽  
V. Tumanskiy
Keyword(s):  
White Matter ◽  
Glutamine Synthetase ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Caudate Nucleus ◽  
Immunohistochemical Study ◽  
Clinical Signs ◽  
Brain Regions ◽  
Progressive Increase ◽  
The Brain

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.

scholarly journals Hepatic Encephalopathy in Two Goat Kids with Common Paternity

2008 ◽  
Vol 20 (6) ◽  
pp. 807-811 ◽  
Author(s):  
Gregory K. Wilkerson ◽  
Monali M. Bera ◽  
Timothy N. Holt ◽  
Robert J. Callan ◽  
Karamjeet Pandher
Keyword(s):  
Hepatic Encephalopathy ◽  
White Matter ◽  
Reference Interval ◽  
Laboratory Diagnostics ◽  
Cell Hyperplasia ◽  
Mental Deterioration ◽  
Mixed Breed ◽  
History Of ◽  
Portal Veins ◽  
The Brain

Two juvenile, intact, female mixed-breed goats from a common sire were presented for periodic neurologic deficits, seizures, and a generalized loss of body condition that occurred over a 4–6-week period. On physical examination, both goats were thin, obtunded, blind, and ataxic. Laboratory diagnostics revealed increased serum bile acids (95 μmol/l; reference interval: 0–50 μmol/l) in one of the goats. Both goats exhibited progressive physical and mental deterioration, and were eventually euthanized. Upon necropsy, no significant macroscopic lesions were noted. Microscopic examination, however, demonstrated hepatocellular atrophy and anomalies in the hepatic microvasculature, including duplication of hepatic arteries, small-to-indistinct portal veins, and oval cell hyperplasia. In addition, spongiform change was microscopically identified throughout the parenchyma of the brain, most notably within the white matter and along the junction of gray and white matter. The diagnosis of congenital portal vein hypoperfusion (suggestive of a portosystemic shunt) with resultant hepatic encephalopathy was proposed in each case based on the characteristic microscopic lesions in conjunction with the signalment and history of the goats. The observation that the affected kids were sired by the same buck suggests a hereditary basis for the condition in these animals as well.

Rapid Alteration of Tau in Oligodendrocytes After Focal Ischemic Injury in the Rat: Involvement of Free Radicals

1997 ◽  
Vol 17 (6) ◽  
pp. 612-622 ◽  
Author(s):  
Elaine A. Irving ◽  
Kazutaka Yatsushiro ◽  
James McCulloch ◽  
Deborah Dewar
Keyword(s):  
White Matter ◽  
Spin Trap ◽  
Focal Cerebral Ischemia ◽  
Subcortical White Matter ◽  
Artery Occlusion ◽  
Time Dependent ◽  
Mk 801 ◽  
Protein Tau ◽  
Glutamate Receptor Antagonists ◽  
Cerebral Artery Occlusion

Glial inclusions containing the microtubule-associated protein tau are present in a variety of chronic neurodegenerative conditions. We now report a rapid and time-dependent increase of tau immunoreactivity within oligodendrocytes after focal cerebral ischemia in the rat. The number of tau positive oligodendrocytes in the ipsilateral subcortical white matter increased six- to eightfold by 40 minutes after permanent middle cerebral artery occlusion (MCAO). Tau was detected using antibodies that label both the N- and C-terminal of the protein, suggesting accumulation of full-length protein within these cells. Pretreatment with the spin trap agent α-phenyl-tert-butyl-nitrone (PBN)(100mg/kg) reduced the number of tau-positive oligodendrocytes by 55% in the subcortical white matter of the ischemic hemisphere compared with untreated animals at 40 minutes after MCAO. In contrast, pretreatment with glutamate receptor antagonists MK-801 (0.5 mg/kg) or 2,3-dihydroxy-6-nitro-7-sulpfamoylbenzo(f)quinoxaline (NBQX) (2 × 30 mg/kg), failed to reduce the number of tau-positive oligodendrocytes after 40 minutes of ischemia. The results indicate that oligodendrocytes respond rapidly to an ischemic challenge and that free radical-mediated mechanisms are involved in the cascade leading to increased tau immunoreactivity.

scholarly journals MRI and MRV features of a patient with Heat Stroke: a case report

2019 ◽  
Author(s):  
Lizhi Cao ◽  
Juan Wang ◽  
Yaxuan Gao ◽  
Yumei Liang ◽  
Jinhua Yan ◽  
...  
Keyword(s):  
White Matter ◽  
Magnetic Resonance ◽  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Heat Stroke ◽  
Internal Capsule ◽  
Subcortical White Matter ◽  
Posterior Limb ◽  
External Capsule ◽  
The Brain

Abstract Background Heat stroke (HS) is a critical illness that can cause multiple organ dysfunction including damage to the central nervous system (CNS), which can be life-threatening in severe cases. The brain image lesions of HS patient with CNS damage has been rarely reported before and usually variable in different cases, causing confusing to doctors when encounter these patients in the clinic. Cerebral venous thrombosis (CVT) is a rare cause of stroke that mostly affects young people and children. The pathogenesis of brain damage caused by HS is complex, CVT may be involved in the pathogenesis of HS with CNS damage. In this manuscript, we report a case of HS with CVT with symmetrical lesions in the bilateral putamen,posterior limb of internal capsule,external capsule, insula lobe, and subcortical white matter inside the brain. Case presentation We introduced a 48-year-old man who suffered from HS in the hot summer. At the time of admission, he showed high body temperature, coma and shock. Later, he had laboratory evidence of rhabdomyolysis syndrome, acute kidney and liver damage, electrolyte imbalance, acid-base balance disorders, and high D-dimer levels. After several days of anti-shock treatment, his level of consciousness has improved but his vision has declined. The cerebral magnetic resonance imaging (MRI) showed symmetrical lesions of the bilateral posterior limb of internal capsule,putamen,external capsule and insula, and subcortical white matter, and cerebral magnetic resonance venography (MRV) showed the formation of deep cerebral venous thrombosis (DCVT). Therefore, the anti-coagulation treatment was given to patient. After timely clinical intervention, the symptom of the patient was gradually improved. Conclusions The case shows that HS can cause CVT. Therefore, we believe that when we need to identify the cerebral MRI findings of HS, early MRV can greatly help the diagnosis of the disease, and can effectively improve the prognosis.

scholarly journals Differential Impact of Plasma Homocysteine Levels on the Periventricular and Subcortical White Matter Hyperintensities on the Brain

2019 ◽  
Vol 10 ◽  
Author(s):  
Kee Ook Lee ◽  
Min-Hee Woo ◽  
Darda Chung ◽  
Jung-Won Choi ◽  
Nam-Keun Kim ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Subcortical White Matter ◽  
Plasma Homocysteine ◽  
Differential Impact ◽  
The Brain

scholarly journals MRI and MRV features of a patient with Heat Stroke: a case report

2019 ◽  
Author(s):  
Lizhi Cao ◽  
Juan Wang ◽  
Yaxuan Gao ◽  
Yumei Liang ◽  
Jinhua Yan ◽  
...  
Keyword(s):  
White Matter ◽  
Magnetic Resonance ◽  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Heat Stroke ◽  
Internal Capsule ◽  
Subcortical White Matter ◽  
Posterior Limb ◽  
External Capsule ◽  
The Brain

Abstract Background Heat stroke (HS) is a critical illness that can cause multiple organ dysfunction including damage to the central nervous system (CNS), which can be life-threatening in severe cases. The brain image lesions of HS patient with CNS damage has been rarely reported before and usually variable in different cases, causing confusing to doctors when encounter these patients in the clinic. Cerebral venous thrombosis (CVT) is a rare cause of stroke that mostly affects young people and children. The pathogenesis of brain damage caused by HS is complex, CVT may be involved in the pathogenesis of HS with CNS damage. In this manuscript, we report a case of HS with CVT with symmetrical lesions in the bilateral putamen,posterior limb of internal capsule,external capsule, insula lobe, and subcortical white matter inside the brain. Case presentation We introduced a 48-year-old man who suffered from HS in the hot summer. At the time of admission, he showed high body temperature, coma and shock. Later, he had laboratory evidence of rhabdomyolysis syndrome, acute kidney and liver damage, electrolyte imbalance, acid-base balance disorders, and high D-dimer levels. After several days of anti-shock treatment, his level of consciousness has improved but his vision has declined. The cerebral magnetic resonance imaging (MRI) showed symmetrical lesions of the bilateral posterior limb of internal capsule,putamen,external capsule and insula, and subcortical white matter, and cerebral magnetic resonance venography (MRV) showed the formation of deep cerebral venous thrombosis (DCVT). Therefore, the anti-coagulation treatment was given to patient. After timely clinical intervention, the symptom of the patient was gradually improved. Conclusions The case shows that HS can cause CVT. Therefore, we believe that when we need to identify the cerebral MRI findings of HS, early MRV can greatly help the diagnosis of the disease, and can effectively improve the prognosis.

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

Pathologia ◽  
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.  

Transport of 3-hydroxy[3-14C]butyrate by dissociated cells from rat brain

1988 ◽  
Vol 255 (2) ◽  
pp. C133-C139 ◽  
Author(s):  
J. T. Tildon ◽  
L. M. Roeder
Keyword(s):  
Rat Brain ◽  
Cellular Level ◽  
Brain Cells ◽  
Maximal Velocity ◽  
System A ◽  
Carrier Mediated Transport ◽  
Dissociated Cells ◽  
Old Rats ◽  
Dissociated Brain Cells ◽  
The Brain

Recent studies suggest that the utilization of oxidizable substrates by the brain may be regulated in part by transport across the plasma membrane. Dissociated brain cells obtained by mechanical disruption of rat brain were used to measure the uptake of 3-hydroxy[3-14C]butyrate. Total uptake revealed two mechanisms (diffusion and a carrier-mediated system). A Lineweaver-Burk plot of the latter component yielded an apparent Km of 1.47 mM and a maximal velocity (Vmax) of 5 nmol.min-1.mg protein-1. The rates of uptake were temperature dependent and were significantly higher at pH 6.2 than at pH 7.4 or 8.2. Preloading the cells and increasing the intracellular concentration of 3-hydroxybutyrate using 12.5 and 25 mM increased the rate of uptake 143 and 206%, respectively, indicative of an accelerative exchange mechanism. Uptake was inhibited approximately 50% by (in mM) 10 phenylpyruvate, 10 alpha-ketoisocaproate, 10 KCN, and 1.5 NaAsO2. Uptake was also decreased by (in mM) 5 lactate, 5 methyl malonic acid, 1 alpha-cyano-4-hydroxycinnamate, and 1 mersalyl. Dissociated brain cells from 14- to 16-day-old rats accumulated 3-hydroxybutyrate at a rate more than two-fold greater than cells from either younger (2-day-old) or older (28-day-old and adult) animals. These data are consistent with the proposal that 3-hydroxybutyrate is taken up by the brain by both diffusion and a carrier-mediated transport system, and they support the hypothesis that transport at the cellular level contributes to the regulation of substrate utilization by the brain.

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