scholarly journals Systemic inflammation and delirium: important co-factors in the progression of dementia

2011 ◽  
Vol 39 (4) ◽  
pp. 945-953 ◽  
Author(s):  
Colm Cunningham

It is widely accepted that inflammation plays some role in the progression of chronic neurodegenerative diseases such as AD (Alzheimer's disease), but its precise role remains elusive. It has been known for many years that systemic inflammatory insults can signal to the brain to induce changes in CNS (central nervous system) function, typically grouped under the syndrome of sickness behaviour. These changes are mediated via systemic and CNS cytokine and prostaglandin synthesis. When patients with dementia suffer similar systemic inflammatory insults, delirium is a frequent consequence. This profound and acute exacerbation of cognitive dysfunction is associated with poor prognosis: accelerating cognitive decline and shortening time to permanent institutionalization and death. Therefore a better understanding of how delirium occurs during dementia and how these episodes impact on existing neurodegeneration are now important priorities. The current review summarizes the relationship between dementia, systemic inflammation and episodes of delirium and addresses the basic scientific approaches currently being pursued with respect to understanding acute cognitive dysfunction during aging and dementia. In addition, despite there being limited studies on this subject, it is becoming increasingly clear that infections and other systemic inflammatory conditions do increase the risk of AD and accelerate the progression of established dementia. These data suggest that systemic inflammation is a major contributor to the progression of dementia and constitutes an important clinical target.

2021 ◽  
Vol 190 ◽  
pp. 553-559
Author(s):  
Irina K. Malashenkova ◽  
Vadim L. Ushakov ◽  
Sergey A. Krynskiy ◽  
Daniil P. Ogurtsov ◽  
Nikita A. Khailov ◽  
...  

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 270 ◽  
Author(s):  
Jai Min Choi ◽  
Odunayo O. Rotimi ◽  
Simon J. O'Carroll ◽  
Louise F.B. Nicholson

Systemic inflammation is associated with neurodegeneration, with elevated interleukin-6 (IL-6) in particular being correlated with an increased risk of dementia. The brain endothelial cells of the blood brain barrier (BBB) serve as the interface between the systemic circulation and the brain microenvironment and are therefore likely to be a key player in the development of neuropathology associated with systemic inflammation. Endothelial cells are known to require soluble IL-6 receptor (sIL-6R) in order to respond to IL-6, but studies in rat models have shown that this is not the case for brain endothelial cells and studies conducted in human cells are limited. Here we report for the first time that the human cerebral microvascular cell line, hCMVEC, uses the classical mIL-6R signalling pathway in response to IL-6 in a concentration-dependent manner as measured by the production of monocyte chemotactic protein (MCP-1). This novel finding highlights a unique characteristic of human brain endothelial cells and that further investigation into the phenotype of this cell type is needed to elucidate the mechanisms of BBB pathology in inflammatory conditions.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 270 ◽  
Author(s):  
Jai Min Choi ◽  
Odunayo O. Rotimi ◽  
Simon J. O'Carroll ◽  
Louise F.B. Nicholson

Systemic inflammation is associated with neurodegeneration, with elevated interleukin-6 (IL-6) in particular being correlated with an increased risk of dementia. The brain endothelial cells of the blood brain barrier (BBB) serve as the interface between the systemic circulation and the brain microenvironment and are therefore likely to be a key player in the development of neuropathology associated with systemic inflammation. Endothelial cells are known to require soluble IL-6 receptor (sIL-6R) in order to respond to IL-6, but studies in rat models have shown that this is not the case for brain endothelial cells and studies conducted in human cells are limited. Here we report for the first time that the human cerebral microvascular cell line, hCMVEC, uses the classical mIL-6R signalling pathway in response to IL-6 in a concentration-dependent manner as measured by the production of monocyte chemotactic protein (MCP-1). This novel finding highlights a unique characteristic of human brain endothelial cells and that further investigation into the phenotype of this cell type is needed to elucidate the mechanisms of BBB pathology in inflammatory conditions.


2011 ◽  
Vol 39 (4) ◽  
pp. 898-901 ◽  
Author(s):  
Clive Holmes ◽  
Joe Butchart

A number of studies demonstrate disturbances of the central innate immune system in AD (Alzheimer's disease). In animal and human studies, there is evidence of close communication between systemic and central innate immune systems. Animal models of neurodegeneration show evidence of an exaggerated central innate immune response following systemic inflammation. Clinical studies of AD show evidence of increased cognitive decline and exaggerated sickness behaviour in response to systemic inflammation. Recognition of this communication pathway offers alternative explanations for a number of recognized risk factors in the development and progression of AD and highlights the potential of the manipulation of systemic innate immunity as a novel therapeutic approach.


2021 ◽  
Vol 22 (1) ◽  
pp. 463
Author(s):  
So Yeong Cheon ◽  
Juhyun Song

Hepatic encephalopathy (HE) is one of the main consequences of liver disease and is observed in severe liver failure and cirrhosis. Recent studies have provided significant evidence that HE shows several neurological symptoms including depressive mood, cognitive dysfunction, impaired circadian rhythm, and attention deficits as well as motor disturbance. Liver disease is also a risk factor for the development of diabetes mellitus. Diabetic encephalopathy (DE) is characterized by cognitive dysfunction and motor impairment. Recent research investigated the relationship between metabolic changes and the pathogenesis of neurological disease, indicating the importance between metabolic organs and the brain. Given that a diverse number of metabolites and changes in the brain contribute to neurologic dysfunction, HE and DE are emerging types of neurologic disease. Here, we review significant evidence of the association between HE and DE, and summarise the common risk factors. This review may provide promising therapeutic information and help to design a future metabolic organ-related study in relation to HE and DE.


2010 ◽  
Vol 2010 (1) ◽  
pp. 5-22
Author(s):  
Ralf Becker

The article examines the relationship between freedom, guilt and responsibility in Dostojewski’s and Sartre’s works. Both attribute a great measure of personal freedom to man. Therefore, they do not tolerate excuses. Whoever is free, carries responsibility and gets caught up in guilt. Dostojewski’s focus is mainly on guilt, Sartre’s is on responsibility. They share the conviction that we can delegate responsibility for our actions or our way of living neither to a whole, of which we are a part, like society (the ,milieu'), nor to a part, for which we are the whole, like the ,brain' or the ,genes'. In that sense, Dostojewski’s and Sartre’s attempts at an ethic of responsibility also offer convincing arguments against determinism.


Author(s):  
M.P. Sutunkova ◽  
B.A. Katsnelson ◽  
L.I. Privalova ◽  
S.N. Solovjeva ◽  
V.B. Gurvich ◽  
...  

We conducted a comparative assessment of the nickel oxide nanoparticles toxicity (NiO) of two sizes (11 and 25 nm) according to a number of indicators of the body state after repeated intraperitoneal injections of these particles suspensions. At equal mass doses, NiO nanoparticles have been found to cause various manifestations of systemic subchronic toxicity with a particularly pronounced effect on liver, kidney function, the body’s antioxidant system, lipid metabolism, white and red blood, redox metabolism, spleen damage, and some disorders of nervous activity allegedly related to the possibility of nickel penetration into the brain from the blood. The relationship between the diameter and toxicity of particles is ambiguous, which may be due to differences in toxicokinetics, which is controlled by both physiological mechanisms and direct penetration of nanoparticles through biological barriers and, finally, unequal solubility.


2020 ◽  
Vol 21 (9) ◽  
pp. 649-660
Author(s):  
Subashini Raman ◽  
Syed Mahmood ◽  
Ayah R. Hilles ◽  
Md Noushad Javed ◽  
Motia Azmana ◽  
...  

Background: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. Methods: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. Results: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. Conclusion: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.


2020 ◽  
Vol 15 (7) ◽  
pp. 602-606
Author(s):  
Kun Ji ◽  
Ling Ding ◽  
Xi Chen ◽  
Yun Dai ◽  
Fangfang Sun ◽  
...  

Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.


2021 ◽  
pp. 1-17
Author(s):  
Stefan Bernhard ◽  
Stefan Hug ◽  
Alexander Elias Paul Stratmann ◽  
Maike Erber ◽  
Laura Vidoni ◽  
...  

A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pH<sub>i</sub>) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pH<sub>i</sub>, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.


Sign in / Sign up

Export Citation Format

Share Document