Sepsis-Associated Encephalopathy

2014 ◽  
Author(s):  
Eric Magalhaes ◽  
Angelo Polito ◽  
Andréa Polito ◽  
Tarek Sharshar
Keyword(s):  
Microglial Activation ◽  
Specific Treatment ◽  
Major Complication ◽  
Endothelial Activation ◽  
Brain Dysfunction ◽  
Biological Mechanisms ◽  
Neurotoxic Effects ◽  
The Central Nervous System ◽  
Alteration Of Consciousness

Brain dysfunction is a major complication of sepsis and is characterized by alteration of consciousness, ranging from delirium to coma and marked electroencephalographic changes. It reflects a constellation of dynamic biological mechanisms, including neurotransmitter imbalance, macro- and microcirculatory dysfunction resulting in ischaemia, endothelial activation, alteration of the blood-brain barrier impairment with passage of neurotoxic mediators, activation of microglial cells within the central nervous system, cumulatively resulting in a neuroinflammatory state. Sepsis-associated brain dysfunction is associated with increased mortality and long-term cognitive decline, whose mechanisms might include microglial activation, axonopathy, or cerebral microinfarction. There is no specific treatment, other than the management of the underlying septic source, correction of physiological and metabolic abnormalities, and limiting the use of medications with neurotoxic effects.

scholarly journals Effects of ZIKV + IgG+ complex on murine microglial cells

2021 ◽  
Author(s):  
Giulia Pinzetta ◽  
Nicole Bernd Becker ◽  
Felipe Krimberg ◽  
Ângela Zanatta ◽  
Laura Siqueira ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Microglial Activation ◽  
Ros Production ◽  
Transplacental Transmission ◽  
Igg Antibodies ◽  
Murine Microglia ◽  
The Central Nervous System ◽  
Complex Methods

Background: Infection by Zika virus (ZIKV) is associated with damage to the Central Nervous System, such as Congenital Zika Syndrome1 . Due to its transplacental transmission, ZIKV induces neuroinflammation and microglial activation, resulting in lesions that can compromise neurodevelopment2-4. The fetus protection can be provided by maternal antibodies. However, this protection is still controversial5 . In this context, it is necessary to elucidate the effects of ZIKV and the mechanisms involved. Objectives: The present work aim to evaluate the role of the ZIKV+IgG+ complex in murine microglia cells (BV2). Design and setting: BV2 were exposed for 24 or 72 hours, to ZIKV, ZIKA-IgG+ or ZIKV+IgG+ complex. Methods: Effects of exposure to treatments were evaluated by MTT, oxidation of DCFHDA (ROS production)6 and mitochondrial membrane potential (Δ∴ϑ), measured by JC-17 assay. Results: It was observed that ZIKV-IgG+ and the ZIKV+IgG+ complex are cytotoxic to microglia, impairing the viability of these cells, altering Δ∴ϑ and inducing the production of ROS, especially in long-term exposure8,9. Negative action mediated by these antibodies may be a result of oxidative stress and a intervention in the Δ∴ϑ. Conclusion: ZIKV-IgG+ antibodies are harmful to microglia and these mechanisms may be related to the potential for ZIKV neuroinflammation.

scholarly journals Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage

2021 ◽  
Vol 15 ◽  
Author(s):  
Fan Wu ◽  
Zongchi Liu ◽  
Ganglei Li ◽  
Lihui Zhou ◽  
Kaiyuan Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Immune Cells ◽  
Brain Dysfunction ◽  
New Ideas ◽  
Negative Role ◽  
The Central Nervous System ◽  
And Oxidative Stress

Subarachnoid hemorrhage (SAH) has a high mortality rate and causes long-term disability in many patients, often associated with cognitive impairment. However, the pathogenesis of delayed brain dysfunction after SAH is not fully understood. A growing body of evidence suggests that neuroinflammation and oxidative stress play a negative role in neurofunctional deficits. Red blood cells and hemoglobin, immune cells, proinflammatory cytokines, and peroxidases are directly or indirectly involved in the regulation of neuroinflammation and oxidative stress in the central nervous system after SAH. This review explores the role of various cellular and acellular components in secondary inflammation and oxidative stress after SAH, and aims to provide new ideas for clinical treatment to improve the prognosis of SAH.

scholarly journals Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation

2021 ◽  
Vol 14 (5) ◽  
pp. 416
Author(s):  
Carolina Araújo Moraes ◽  
Camila Zaverucha-do-Valle ◽  
Renaud Fleurance ◽  
Tarek Sharshar ◽  
Fernando Augusto Bozza ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Current Knowledge ◽  
Brain Dysfunction ◽  
Regulatory Mechanisms ◽  
Molecular Pathways ◽  
Neurological Manifestations ◽  
The Central Nervous System ◽  
The Brain

Frequently underestimated, encephalopathy or delirium are common neurological manifestations associated with sepsis. Brain dysfunction occurs in up to 80% of cases and is directly associated with increased mortality and long-term neurocognitive consequences. Although the central nervous system (CNS) has been classically viewed as an immune-privileged system, neuroinflammation is emerging as a central mechanism of brain dysfunction in sepsis. Microglial cells are major players in this setting. Here, we aimed to discuss the current knowledge on how the brain is affected by peripheral immune activation in sepsis and the role of microglia in these processes. This review focused on the molecular pathways of microglial activity in sepsis, its regulatory mechanisms, and their interaction with other CNS cells, especially with neuronal cells and circuits.

The Impact of Timing of Microglial Activation by Inflammation and Hypoxia Regarding Additive Neurotoxic Effects

2014 ◽  
Vol 45 (S 01) ◽  
Author(s):  
S. Jung ◽  
D. Frey ◽  
F. Brackmann ◽  
M. Richter-Kraus ◽  
R. Trollmann
Keyword(s):  
Microglial Activation ◽  
Neurotoxic Effects ◽  
The Impact

Herbal Medicine for Glioblastoma: Current and Future Prospects

2020 ◽  
Vol 16 (8) ◽  
pp. 1022-1043
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Mustafa A. Hatiboglu
Keyword(s):  
Cell Proliferation ◽  
Survival Rates ◽  
Standard Of Care ◽  
Natural Compounds ◽  
Treatment Modalities ◽  
Normal Brain ◽  
The Central Nervous System ◽  
Cycle Regulation ◽  
Immense Potential

Background: Glioblastoma is one of the most aggressive and devastating tumours of the central nervous system with short survival time. Glioblastoma usually shows fast cell proliferation and invasion of normal brain tissue causing poor prognosis. The present standard of care in patients with glioblastoma includes surgery followed by radiotherapy and temozolomide (TMZ) based chemotherapy. Unfortunately, these approaches are not sufficient to lead a favorable prognosis and survival rates. As the current approaches do not provide a long-term benefit in those patients, new alternative treatments including natural compounds, have drawn attention. Due to their natural origin, they are associated with minimum cellular toxicity towards normal cells and it has become one of the most attractive approaches to treat tumours by natural compounds or phytochemicals. Objective: In the present review, the role of natural compounds or phytochemicals in the treatment of glioblastoma describing their efficacy on various aspects of glioblastoma pathophysiology such as cell proliferation, apoptosis, cell cycle regulation, cellular signaling pathways, chemoresistance and their role in combinatorial therapeutic approaches was described. Methods: Peer-reviewed literature was extracted using Pubmed, EMBASE Ovid and Google Scholar to be reviewed in the present article. Conclusion: Preclinical data available in the literature suggest that phytochemicals hold immense potential to be translated into treatment modalities. However, further clinical studies with conclusive results are required to implement phytochemicals in treatment modalities.

scholarly journals Self-buffering capacity of a human sulfatase for central nervous system delivery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi Wen ◽  
Nazila Salamat-Miller ◽  
Keethkumar Jain ◽  
Katherine Taylor
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Buffering Capacity ◽  
The Self ◽  
High Concentration ◽  
Formulation Design ◽  
The Central Nervous System ◽  
Therapeutic Enzymes ◽  
Intrathecal Space

AbstractDirect delivery of therapeutic enzymes to the Central Nervous System requires stringent formulation design. Not only should the formulation design consider the delicate balance of existing ions, proteins, and osmolality in the cerebrospinal fluid, it must also provide long term efficacy and stability for the enzyme. One fundamental approach to this predicament is designing formulations with no buffering species. In this study, we report a high concentration, saline-based formulation for a human sulfatase for its delivery into the intrathecal space. A high concentration formulation (≤ 40 mg/mL) was developed through a series of systematic studies that demonstrated the feasibility of a self-buffered formulation for this molecule. The self-buffering capacity phenomenon was found to be a product of both the protein itself and potentially the residual phosphates associated with the protein. To date, the self-buffered formulation for this molecule has been stable for up to 4 years when stored at 5 ± 3 °C, with no changes either in the pH values or other quality attributes of the molecule. The high concentration self-buffered protein formulation was also observed to be stable when exposed to multiple freeze–thaw cycles and was robust during in-use and agitation studies.

scholarly journals Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain

2018 ◽  
Vol 10 (471) ◽  
pp. eaan0237 ◽  
Author(s):  
Diego F. Niño ◽  
Qinjie Zhou ◽  
Yukihiro Yamaguchi ◽  
Laura Y. Martin ◽  
Sanxia Wang ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Microglial Activation ◽  
Gastrointestinal Disease ◽  
Cognitive Impairments ◽  
High Mobility ◽  
Neurological Dysfunction ◽  
Mucosal Inflammation ◽  
Signaling Axis ◽  
The Brain

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies. We have recently shown that NEC development is dependent on the expression of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium, whose activation by bacteria in the newborn gut leads to mucosal inflammation. Here, we hypothesized that damage-induced production of TLR4 endogenous ligands in the intestine might lead to activation of microglial cells in the brain and promote cognitive impairments. We identified a gut-brain signaling axis in an NEC mouse model in which activation of intestinal TLR4 signaling led to release of high-mobility group box 1 in the intestine that, in turn, promoted microglial activation in the brain and neurological dysfunction. We further demonstrated that an orally administered dendrimer-based nanotherapeutic approach to targeting activated microglia could prevent NEC-associated neurological dysfunction in neonatal mice. These findings shed light on the molecular pathways leading to the development of NEC-associated brain injury, provide a rationale for early removal of diseased intestine in NEC, and indicate the potential of targeted therapies that protect the developing brain in the treatment of NEC in early childhood.

Possible reason for preferential damage to renal tubular epithelial cells evoked by amphotericin B.

1996 ◽  
Vol 40 (5) ◽  
pp. 1116-1120 ◽  
Author(s):  
I Walev ◽  
S Bhakdi
Keyword(s):  
Epithelial Cells ◽  
Amphotericin B ◽  
Important Determinant ◽  
Major Complication ◽  
Toxic Action ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Recovery Mechanisms ◽  
Renal Tubular

An important determinant of nephrotoxicity, which is the major complication of long-term amphotericin B treatment, is dysfunction of distal tubular epithelial cells. The underlying cause for this rather selective damage to the cells is unknown. In the present investigation, it was shown that kidney epithelial cells were initially damaged by amphotericin B at concentrations of 2.5 to 10 micrograms/ml, as demonstrable by a dramatic drop in cellular K+ levels. Cells could recover from the initial toxic action of the polyene if they were kept in medium of neutral pH, and cellular K+ levels returned to normal after 6 h. However, the recovery mechanisms failed at lower pHs of 5.6 to 6.0. At low pHs, cells became progressively depleted of ATP; they leaked lactate dehydrogenase and became irreversibly damaged after approximately 6 h. The possibility that the low pH characteristic of the distal tubulus lumen renders the renal epithelial cells particularly vulnerable to the toxic action of amphotericin B is raised. The concept is in line with an earlier report that alkalization ameliorates amphotericin B nephrotoxicity in rats.

scholarly journals Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Song Cao ◽  
Daniel W. Fisher ◽  
Guadalupe Rodriguez ◽  
Tian Yu ◽  
Hongxin Dong
Keyword(s):  
Spinal Cord ◽  
Locus Coeruleus ◽  
Microglial Activation ◽  
Healthy Aging ◽  
Cell Types ◽  
Norepinephrine System ◽  
Protective Processes ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Abstract Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

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