The scientists injected a fluorescent tracer, FITC, into a large reservoir of CSF called the cisterna magna.

This enabled the scientists to detect CSF as it circulated through the brain and diffused into the interstitial space between neurons.

The scientists observe that the CSF in sleeping mice flows robustly along arteries and diffuses into the surface of the brain (the parenchyma).

The scientists awaken sleeping mice and inject a second tracer (also small) into their CSF.

The scientists observe far less CSF flow along arteries and into the brain. This suggests that wakefulness exerts a powerful and rapid effect on CSF circulation.

This experiment compares two arousal states within the same mouse, rather than comparing the two states in two different mice. This kind of experimental design minimizes the impact of genetic and environmental variability between mice and makes this study extremely powerful.

The scientists have already demonstrated that CSF circulation is reduced when they wake a sleeping mouse.

However, it is possible that this is only true when a mouse is awakened in the middle of its sleep cycle, or that it is a short-lived effect that only matters during the first several minutes of wakefulness.

The scientists expanded their finding by injecting tracer into awake mice and then anesthetizing them.

An Analysis of Variance (ANOVA) is a statistical method for determining whether multiple groups being studied are truly different from each other.

"n = 6 mice" means that six mice were compared in total; this is a small sample, but because of the powerful design of their study (comparing arousal states within the same mouse), the scientists are able to detect significant differences between groups.

Aβ and an inert tracer, inulin, are removed from the brain about twice as efficiently in sleeping mice compared with awake mice.

This suggests that sleep may play a crucial role in the removal of harmful waste products and proteins which accumulate during metabolic processes.

Additionally, it suggests that the neurotoxicity observed in both Alzheimer's disease and chronic insomnia could be due in part to a failure in the sleep-driven expansion of the interstitial space.

In order to test whether their findings may be relevant for understanding Alzheimer's disease (AD), the scientists wanted to determine if the clearance (removal) of beta amyloid, Aβ, a protein that accumulates during AD, was more or less efficient during sleep.

The scientists injected small amounts of a slightly radioactive form of Aβ, then waited for between 10 minutes and 4 hours, giving the brain an opportunity to remove the Aβ.

The radioactive label is believed to not impact the clearance of Aβ, and allowed the authors to determine how much of the Aβ protein remained in the brain using a gamma counter.

The system that clears waste from the brain.

There is less CSF circulation in the brain when a mouse is awake.

The scientists confirmed that awake mice showed reduced influx of CSF compared to anesthetized mice.

Together, with the previous experiment, this finding compellingly demonstrates that arousal state has a powerful effect on the influx of CSF through a mouse's brain.

Small molecular weight tracers are small, and can therefore diffuse easily.

The tracer used here, FITC, is only 30% smaller than the protein the scientists later examine, beta amyloid.

FITC's ability to diffuse and penetrate into the interstitial space should, therefore, be similar to beta amyloid, making this a powerful experiment.

The tracer will travel through the brain just as beta amyloid would.

These are two methods the scientists used to ensure the mice were awake or sleeping.

Electrocorticography measures brain activity

Electromyography measures muscle activity

If both were high, the mouse was considered awake

If both were low, the mouse was considered sleeping

The authors are looking to see if CSF influx (part of the convective exchange) is different between:

awake mice sleeping mice anesthetized mice

"in vivo" is Latin for "within the living."

Here, it indicates that the experiment was done in a living mouse.

It has always been challenging to perform experiments on living animals; there are many technological, practical, and ethical concerns which generally limit the precision with which experiments can be conducted.

For example, in order to see beyond the surface of mouse's brain, we have always needed to cut the brain into thin sections, and therefore need to euthanize the mouse.

With the invention of two-photon imaging, it became possible to image noninvasively (without the need to euthanize) deep into a mouse's brain, unlocking powerful experiments such as those performed in this paper.

A video describing the glymphatic system, a paravascular pathway that facilitates the clearance of waste and solutes from the cerebrospinal fluid and interstitial fluid of the brain.

http://www.jci.org/videos/4

This illustrates how scientists ask questions.

The authors take an observed phenomenon (sleep) and carefully form testable hypotheses about its function.

They combine their observation that sleep is restorative and dysregulated sleep is associated with mental illness, with their knowledge of the glymphatic system.

They hypothesize a connection between the two, which they carefully test in well-designed experiments.

They choose powerful methods for data collection and analysis, making comparisons within individuals to minimize variability, and systematically recording data at a variety of time points and conditions to increase their probability of answering their questions.

Finally, they connect their findings into a general model for how sleep, arousal, and glymphatic function could interplay in normally functioning as well as diseased brains.

Scientists previously discovered that Aβ levels vary in a daily cycle, and that Aβ levels in the interstitial fluid rise as humans and mice spend more time awake.

This surprising finding could add to our understanding of diseases, including Alzheimer's disease and insomnia.

However, this result says nothing about the mechanism — that is, increased Aβ during wakefulness could be owing to increased production, decreased degradation, reduced clearance, or processes like synaptic function that are related to both sleep and Aβ.

The current article addresses this ambiguity directly.

This is the convective exchange described in the abstract.

Convective exchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF) is the basic mechanism by which the glymphatic system clears metabolites from the interstitial fluid.

ISF enters the brain along arteries, and flows into the interstitial space, replenishing CSF.

CSF flows into interstitial vessels along veins, carrying waste metabolites and proteins with it.

These two processes create net flows of CSF — in essence, small rivers of CSF flow, beginning with an ISF-to-CSF exchange near arteries, and ending with a CSF to ISF exchange near veins.

The combination of these rivers and the exchanges are called convective exchange.

The lymphatic system does not extend to the brain. The brain has it's own system for clearing waste.

In the rest of the body, the lymphatic system "cleans" up waste and moves it to the liver where it is destroyed.

Peripheral tissue refers to the entire body outside of the brain.

The body has the highly specialized lymphatic system for transporting interstitial metabolites (waste) and proteins to the liver.

The brain uses a different mechanism, recently discovered and dubbed the "glymphatic system." The glymphatic system is basically a cleaning system for the brain.

space between individual brain cells

Additional proteins involved in neurodegenerative diseases.

Beta amyloid (Aβ) is a small protein involved in Alzheimer's disease (AD).

Large clumps of Aβ protein (called plaques) are very prevalent in Alzheimer's disease, and are thus the focus of an enormous amount of research.

It remains unclear what, if any, the causal connection is between Aβ and Alzheimer's disease, but clinical trials are under way to attempt to treat Alzheimer's disease by directly targeting Aβ plaques.

Neurodegenerative disease refers to several different diseases that impact the brain. Examples of neurodegenerative diseases include:

• Parkinson’s
• Alzheimer’s
• Huntington’s disease.

In all neurodegenerative diseases, there is a progressive degeneration and/or death of brain cells.

Years of scientific research has already discovered this about sleep.

The scientists are asking two questions in this study:

"why do we need sleep?"

"why do we feel bad if we do not get enough sleep?"

The brain uses sleep to wash away the waste toxins built up during a hard day's thinking, researchers have shown.

http://www.bbc.com/news/health-24567412

Beta amyloid (Aβ) is a small protein involved in Alzheimer's disease (AD).

Large clumps of Aβ protein (called plaques) are very prevalent in Alzheimer's disease, and are thus the focus of an enormous amount of research.

It remains unclear what, if any, the causal connection is between Aβ and Alzheimer's disease, but clinical trials are under way to attempt to treat Alzheimer's disease by directly targeting Aβ plaques.

Interstitial fluid (ISF) is the fluid responsible for carrying waste and proteins out of the CSF (cerebrospinal fluid) and away from the brain.

ISF flows in vessels surrounding arteries and veins, transporting waste away from the interstitial space (space between individual brain cells) for degradation.

ISF is continually exchanged for CSF near arteries and then replenished by CSF removal near veins, establishing a flow throughout the brain.

Cerebrospinal fluid, or CSF, is the fluid which circulates through the brain and spine.

It is the extracellular solution (fluid) surrounding all neurons in the central nervous system (brain and spine), so its composition must be carefully controlled to maintain proper function of neurons and brain cells.

Brain may flush out toxins during sleep

A NIH-funded study suggests sleep clears brain of damaging molecules associated with neurodegeneration

http://www.nih.gov/news/health/oct2013/ninds-17.htm

Convective exchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF) is the basic mechanism by which the glymphatic system clears metabolites from the interstitial fluid.

ISF enters the brain along arteries, and flows into the interstitial space, replenishing CSF.

CSF flows into interstitial vessels along veins, carrying waste metabolites and proteins with it.

These two processes create net flows of CSF — in essence, small rivers of CSF flow, beginning with an ISF-to-CSF exchange near arteries, and ending with a CSF to ISF exchange near veins.

The combination of these rivers and the exchanges are called convective exchange.

Interstitial space in this paper refers to the space surrounding cells in the brain, and the space between the brain and the thin layers (meninges) which surround it.

Damaged proteins and metabolic waste may be secreted into the cerebrospinal fluid (CSF), where they accumulate in the interstitial space.

These waste products are meant to be cleared, or removed, by fluid exchange through the glymphatic system.

A larger interstitial space would be expected to clear waste products faster, since there would be less resistance to diffusion and fluid motion.

Diffusion is the random movement of particles, which, on average, causes high-density pockets of particles to spread out into areas of lower density.

The final concentration of the particles after diffusion depends on the size of the container in which they diffuse: Cut an onion in a small kitchen and the fumes may be felt by everyone, but cut it in a sports arena and nobody will notice as the odor diffuses harmlessly.

In this paper, the authors inject small amounts of a substance, tetramethylammonium (TMA), into the interstitial space.

By measuring the concentration of TMA after diffusion, they can estimate the volume of the space in which the TMA is diffusing.

Metabolic processes like the production and use of energy, protein creation, and degradation, etc., all involve the generation of by-products, some of which can be harmful.

Metabolic homeostasis refers to the active process of maintaining proper, nonharmful levels of molecules produced during cell metabolism.

annotating the word plant.

It has been observed that after the introduction of measles vaccination there was a drop in childhood death rates not entirely explainable by the prevention of just measles. Others have observed an immunosuppression effect after measles infection and attempted to study this via molecular virology/immunology as well as epidemiologically by studying measles incidence in low-income countries. This paper takes a unique approach to study the phenomenon by examining high-income countries with overall lower incidence of infectious disease in an attempt to remove the complicating factors of increased childhood mortality in the low-income countries. By doing so the duration of immunomodulation (approximately 2.5 years) is revealed.

Researchers have also noted that there are differences in the gender of the child that can change how protective the Measles vaccine is at protecting against other illnesses.

WHO and other researchers have found that the Measles vaccine, and other live vaccines, can have effects of childhood mortality not associated with the vaccine target. This reference is a review of some of the studies done in the past to try and better understand this off target effect.

Scientists use a sample from Bangladesh to look at data similar to the results of this paper. They also find that Measles vaccinating reduces childhood mortality not due to Measles, specifically from diarrhea and oedema. However, the data used in their analysis is only one sample of a population and is confounded by some study control issues.

Almost all of us, one day wake up with the noise of the construction coming outside our houses and wonder what is going on. One of the reasons for this unprecedented noise could be the replacement of sewer pipes, but why are they being replaced? Sewer corrosion is one of the main reasons and primarily, sulfate is to be blamed for corrosion. In this paper, authors investigated the main source of sulfate in our sewer systems. Does the majority of sulfate come from the nature or is it caused by human interference? They found out that addition of a coagulant named "aluminum sulfate" during drinking water treatment makes the highest impact on sulfate presence in sewer systems.

hello!

test test test