New ads.

Showing posts with label inflammation. Show all posts
Showing posts with label inflammation. Show all posts

Saturday, November 23, 2019

Link between inflammation and mental sluggishness shown in new study

Brain fog abstract concept illustration

Scientists at the University of Birmingham in collaboration with the University of Amsterdam have uncovered a possible explanation for the mental sluggishness that often accompanies illness.
An estimated 12M UK citizens have a chronic medical condition, and many of them report severe mental fatigue that they characterize as 'sluggishness' or 'brain fog'. This condition is often as debilitating as the disease itself.
A team in the University's Centre for Human Brain Health investigated the link between this mental fog and inflammation -- the body's response to illness. In a study published in Neuroimage, they show that inflammation appears to have a particular negative impact on the brain's readiness to reach and maintain an alert state.
Dr Ali Mazaheri and Professor Jane Raymond of the University's Centre for Human Brain Health, are the senior authors of the study. Dr Mazaheri says: "Scientists have long suspected a link between inflammation and cognition, but it is very difficult to be clear about the cause and effect. For example, people living with a medical condition or being very overweight might complain of cognitive impairment, but it's hard to tell if that's due to the inflammation associated with these conditions or if there are other reasons."
"Our research has identified a specific critical process within the brain that is clearly affected when inflammation is present."
The study focussed specifically on an area of the brain which is responsible for visual attention. A group of 20 young male volunteers took part and received a salmonella typhoid vaccine that causes temporary inflammation but has few other side effects. They were tested for cognitive responses to simple images on a computer screen a few hours after the injection so that their ability to control attention could be measured. Brain activity was measured while they performed the attention tests.
On a different day, either before or after, they received an injection with water (a placebo) and did the same attention tests. On each test day they were unaware of which injection they had received. Their inflammation state was measured by analysing blood taken on each day.
The tests used in the study assessed three separate attention processes, each involving distinct parts of the brain. These processes are: "alerting" which involves reaching and maintaining an alert state; "orienting" which involves selecting and prioritising useful sensory information; and "executive control" used to resolving what to pay attention to when available information is conflicting.
The results showed that inflammation specifically affected brain activity related to staying alert, while the other attention processes appeared unaffected by inflammation.
"These results show quite clearly that there's a very specific part of the brain network that's affected by inflammation," says Dr Mazaheri. "This could explain 'brain fog'."
Professor Raymond says, "This research finding is major step forward in understanding the links between physical, cognitive, and mental health and tells us that even the mildest of illnesses may reduce alertness."
Dr Leonie Balter the first author of the study which was completed as part of her PhD, concluded : "Getting a better understanding of the relationships between inflammation and brain function will help us investigate other ways to treat some of these conditions. For example, further research might show that patients with conditions associated with chronic inflammation, such as obesity, kidney disease or Alzheimer's, could benefit from taking anti-inflammatory drugs to help preserve or improve cognitive function."
"Furthermore, subtle changes in brain function may be used as an early marker cognitive deterioration in patients with inflammatory diseases."
The next step for the team will be to test the effects of inflammation on other areas of brain function such as memory.

Story Source:
Materials provided by University of BirminghamNote: Content may be edited for style and length.

Friday, November 22, 2019

Probing the role of an inflammation resolution sensor in obesity and heart failure

After heart attack injury, several fatty-acid-derived bioactive molecules -- including one called resolvin D1 -- play an essential signaling role to safely clear inflammation and help repair heart muscle. The mechanism of how this resolution occurs is not well-understood.
There is a receptor on the surface of many immune cells called ALX/FRP2, and in models of atherosclerosis, ALX/FPR2 is known to act as a sensor to help resolve inflammation.
In a 2015 study using a mouse model, University of Alabama at Birmingham researcher Ganesh Halade, Ph.D., observed that, after heart attack injury, ALX/FPR2 was highly expressed in immune myeloid cells and was activated by resolvin D1 in immune cells in the spleen and in immune cells at the heart attack site. The result was an expedited resolution of the heart attack injury. Resolvin D1 is one of the omega 3 fatty-acid metabolites known as specialized pro-resolving mediators, or SPMs, that help clear inflammation.
Now, Halade and colleagues at UAB, Boston and France have used mice that completely lack ALX/FPR2 to learn more about the pathways this resolution sensor uses to target inflammation. Such knowledge will help in finding treatments to delay the human heart failure that often follows a heart attack.
Before beginning the mouse studies, Halade and colleagues examined heart muscle tissue from patients with heart failure. They found that ALX/FPR2 was plentiful in these human ischemic hearts, and it was located in the cytoplasm of the myocardium cells. In contrast, in healthy human heart tissue, ALX/FPR2 was limited to the cell membrane. To learn more, they then expanded study of the precise and comprehensive role of the resolution receptor using mice having an ALX/FPR2 gene deletion.
The researchers found that mice lacking ALX/FPR2 showed spontaneous, age-related obesity. With the obesity, the ALX/FPR2-null mice developed heart disease that weakened the heart's ability to pump blood, and they had a shortened lifespan with aging. The aging mice also developed kidney inflammation, as shown by increased inflammation markers like NGAL, TNF-alpha and CCL2, and elevated plasma creatinine levels.
After a heart attack in normal mice, leukocyte immune cells in the spleen produce SPMs. However, in the ALX/FPR2-null mice, the researchers found lower levels of SPMs in the heart and the spleen after heart attack, indicative of non-resolving inflammation. Halade says this suggested impaired cross-talk between the injured heart and splenic leukocytes, a cross-talk that is required for the resolution of inflammation. In addition to the lower levels of SPMs, the ALX/FPR2-null mice showed dysregulation of several immune responsive enzymes -- lower levels of LOX enzymes and increased levels of the pro-inflammatory COX-1 and COX-2 enzymes.
Finally, the ALX/FPR2-null mice showed impairment of activated macrophage cells to phagocytose -- that is, to "eat" infecting microbes or dead human cells, one of the macrophage's prime functions. After heart attack, the ALX/FPR2-null mice had increased numbers of neutrophils, the first phagocytic responders after heart injury, in both the spleen and the left ventricle of the heart. Also, there were reduced numbers of reparative macrophages in both the spleen and the heart.
Altogether, says Halade, an associate professor in the UAB Department of Medicine Division of Cardiovascular Disease, these findings demonstrate the integrative role of ALX/FPR2 as a primary target to manage cardiometabolic health, inflammation-resolution processes and cardiorenal syndrome in aging.

Story Source:
Materials provided by University of Alabama at BirminghamNote: Content may be edited for style and length.