Transparent Brains Ready for Study Researchers at the RIKEN Brain science Institute in Japan have developed a new technique for creating transparent tissue that can be used to illuminate 3d brain anatomy at very high resolutions.
Published in Nature Neuroscience, the work showcases the new technology and its practical importance in clinical science by showing how it has given new insights into Alzheimer disease plaques. he usefulness of optical clearing techniques can be measured by their ability to gather
called Scales, is a real and practical way to see through brain and body tissue. In recent years, generating see-through tissue process called optical clearingas become a goal for many researchers in life sciences because of its potential to reveal complex structural details of our bodies, organs,
we could create transparent brains with minimal tissue damage, that can handle both florescent and immunohistochemical labeling techniques,
The new technique creates transparent brain samples that can be stored in Scales solution for more than a year without damage.
and brains are firm enough to permit the micron-thick slicing necessary for more detailed analyses. he real challenge with optical clearing is at the microscopic level,
the researchers put the technique to practical use by visualizing in 3d the mysterious iffuseplaques seen in the postmortem brains of Alzheimer disease patients that are typically undetectable using 2d imaging.
but showed extensive association with microglia obile cells that surround and protect neurons. Another example of Scales practical application came from examining the 3d positions of active microglial cells and amyloid beta plaques.
While some scientists suggest that active microglial cells are located near plaques a detailed 3d reconstruction and analysis using Scales clearing showed that association with active microglial cells occurs early in plaque development,
and pinpointing structural changes that characterize other brain diseases. t
#Researchers Identify Three Distinct Subtypes of Alzheimer Disease Alzheimer disease, long thought to be a single disease,
and appears more widely distributed across the brain than the other subtypes of Alzheimer. It typically does not seem to cause memory loss at first,
has shown that a specific molecule controls morphine receptor signaling in a small group of brain cells.
Using genetically modified animal models lacking a particular RGS PROTEIN called RGS7, a protein abundant in the brain,
RGS7 appears to exert its effects by regulating morphine-induced changes in excitability of neurons and plasticity of synapseshe ability of the synapse, the junction between two nerve cells,
to change its function. his study reveals a unique modulatory role of RGS7 in a brain region-specific action to morphine use
Autism spectrum disorder is a range of complex neurodevelopmental disorders affecting 2 percent of U s. children.
In the brain, calcium is used to communicate information within and between neurons and it activates a host of other cell functions,
neuronal excitability and neurotransmitter release areas known to be dysfunctional in ASD. e propose that the proper function of this channel
and its signaling pathway is critical for normal performance of neurons and that this signaling pathway represents a key ubin the pathogenesis of ASD,
said Parker, a fellow of London Royal Society and UCI professor of neurobiology & behavior, who studies cellular calcium signaling.
To see if IP3R function is altered across the autism spectrum, clinical researchers at The Center for Autism & Neurodevelopmental Disorders
specifically how it regulates the level of neuron excitability. The brains of people who have autism show signs of hyperexcitability,
which is seen also in epilepsy, a disorder increasingly found to be associated with ASD. Cells from individuals who have depressed autism exhibit levels of calcium signaling
and to be involved in brain formation, but has now been identified as a key part of photoreceptor proteins the structures that allow organisms to sense
Researchers at USC and Wake Forest Baptist Medical center have developed a brain prosthesis that is designed to help individuals suffering from memory loss.
which includes a small array of electrodes implanted into the brain, has performed well in laboratory testing in animals
Signals and sensory input When your brain receives sensory input, it creates a memory in the form of a complex electrical signal that travels through multiple regions of the hippocampus,
the memory center of the brain. At each region, the signal is encoded re until it reaches the final region as a wholly different signal that is sent off for long-term storage.
If there damage at any region that prevents this translation then there is the possibility that long-term memory will not be formed.
With the permission of patients who had implanted electrodes in their hippocampi to treat chronic seizures,
Hampson and Deadwyler read the electrical signals created during memory formation at two regions of the hippocampus,
and read how the signals generated from the first region of the hippocampus were translated into signals generated by the second region of the hippocampus.
Drawing of a brain with a lightening bolt inside it. In hundreds of trials conducted with nine patients,
or replace the function of a damaged part of the brain, Hampson said. In its next step, the team will attempt to send the translated signal back into the brain of a patient with damage at one of the regions
in order to try to bypass the damage and enable the formation of an accurate long-term memory
#Uncovering Clues About Abnormal Embryo Development with Artificial intelligence Melanoma-like cells in tadpoles may mimic variability in human responses to cancer stimuli.
#Noninvasive Brain Palpation May Soon Be Possible If there is one technique used by the physician to explore the human body during every medical examination
however, the brain cannot be palpated without using a highly invasive procedure (craniotomy, or opening the skull),
it could be used in the early diagnosis of brain tumours or Alzheimer disease. This work is published in PNAS.
However, this method cannot be applied to the brain, which, doubly protected by the cranium and cerebrospinal fluid, is difficult for externally applied waves to access.
It is therefore impossible to directly or indirectly palpate the brain, something that greatly complicates the work of neurosurgeons.
On the other hand, the brain is the seat of natural vibrations created by the blood pulsating in the arteries and the circulating cerebrospinal fluid.
There remained a significant unprecedented challenge: how to capture this complex field of natural shear waves,
have succeeded in detecting natural shear waves in the brain using computational techniques borrowed from seismologists
thus able to build images of the brain elasticity. f this method can be developed for clinical use,
since making the brain vibrate is quite painful at the moment. Of course, this method will be complementary to those that already exist
multiple sclerosis and hydrocephalus involve changes in the stiffness of the brain tissues. This new technique allows their detection,
and could be used to avoid brain biopsies. his method for palpating the brain could have other areas of application,
The experimental demonstration is conducted in a calibrated phantom and in vivo in the brain of two healthy volunteers.
Potential applications of this rain palpationapproach for characterizing brain anomalies and diseases are foreseen. o
#Single Drop of Blood in Brain Can Trigger Immune response Akin to Multiple sclerosis Disruption of the blood-brain barrier triggers a cascade of events that results in autoimmunity and brain damage characteristic of multiple sclerosis.
A new study from the Gladstone Institutes shows that a single drop of blood in the brain is sufficient to activate an autoimmune response akin to multiple sclerosis (MS). This is the first demonstration that introduction of blood in the healthy brain
is sufficient to cause peripheral immune cells to enter the brain, which then go on to cause brain damage.
A break in the blood-brain barrier (BBB) allows blood proteins to leak into the brain and is a key characteristic of MS,
a disabling autoimmune disease of the brain and spinal cord. However, it was unclear whether the BBB disruption caused the autoimmune response
They discovered that injecting just one drop of blood into the brain set off the brain immune response,
kick-starting a chain reaction that resulted in inflammation and myelin damage. Myelin is the protective sheath that insulates nerve fibers in the brain,
and it is the primary site of injury in MS. What more, the scientists were able to pinpoint a specific protein in the blood, the blood-clotting factor fibrinogen,
Fibrinogen activated the brain immune cells called microglia, and caused them to send out signals summoning peripheral immune cells from other parts of the body to the brain.
When these peripheral immune cellsacrophages and T cellsntered the brain, they attacked myelin. ur results provide the first evidence that blood promotes T cell responses against the brain,
says first author Jae Kyu Ryu, Phd, a staff research scientist at the Gladstone Institutes. ot only did we confirm that the presence of blood in the brain recruits peripheral immune cells to the area,
which is sufficient to cause myelin destruction, we also identified fibrinogen as the critical protein driving this process.
To confirm their findings the scientists deleted the fibrinogen receptor (complement receptor 3 or CD11B/CD18) on microglia,
thereby preventing fibrinogen from activating the cells. Inhibiting this interaction blocked the autoimmune process, stopping the microglia from signaling to the peripheral immune cells and averting myelin damage and inflammation.
The researchers are now attempting to block fibrinogen using biological and small-molecule approaches as potential new therapies to suppress autoimmunity directed against the brain,
dampening inflammation caused by microglia and T cells. Researchers discovered that injecting just one drop of blood into the brain set off the brain immune response,
kick-starting a chain reaction that resulted in inflammation and myelin damage. Myelin is the protective sheath that insulates nerve fibers in the brain
and it is the primary site of injury in MS. Image is for illustrative purposes only. hese findings question a long-held paradigm that myelin-specific T cells initiate inflammation in the brain through activation of microglia
and brain macrophages, says Scott Zamvil, MD, Phd, a professor of neurology at the University of California,
San francisco and co-author on the paper. his study demonstrates that the original paradigm may also occur in reverse.
Namely, initial activation of microglia and brain macrophages may activate T cells. The scientists say that having a model of blood-induced brain inflammation is a valuable tool
as it can be used to screen new drugs. These mechanisms may occur not only in autoimmune disorders,
but also in other brain diseases that involve inflammation or a break in the BBB, including traumatic brain injury, stroke, Alzheimer disease,
and other dementias e
#Blood test to Detect Alzheimer Disease Close to Development Early detection presents new opportunities to slow or perhaps even halt disease progression.
Researchers from the Rowan University School of Osteopathic Medicine are nearing development of a blood test that can accurately detect the presence of Alzheimer disease,
which would give physicians an opportunity to intervene at the earliest, most treatable stage. Robert Nagele, Phd, presented his team most recent findings October 18 at OMED 15 in Orlando.
As blood vessels in the brain weaken or become brittle with age, they begin to leak,
which allows plasma components including brain-reactive autoantibodies into the brain. There, the autoantibodies can bind to neurons
and accelerate the accumulation of beta amyloid deposits, a hallmark of Alzheimer pathology. The blood test developed by Dr. Nagele has shown also promise in detecting other diseases,
In Alzheimer, the brain begins to change years before symptoms emerge. Detecting Alzheimer antibodies at the preclinical stage would give patients an opportunity to work with their physician to make lifestyle changes
Researchers at Massachusetts Eye and Ear/Harvard Medical school and Boston University have shown successfully neuroprotection in a Parkinson mouse model using new techniques to deliver drugs across the naturally impenetrable blood-brain barrier.
lend hope to patients around the world with neurological conditions that are difficult to treat due to a barrier mechanism that prevents approximately 98 percent of drugs from reaching the brain
and central nervous system. e are developing a platform that may eventually be used to deliver a variety of drugs to the brain,
seizure disorders and many other conditions affecting the brain and nervous system down the road. Using nasal mucosal grafting,
researchers delivered glial derived neurotrophic factor (GDNF), a therapeutic protein in testing for treating Parkinson disease, to the brains of mice.
They showed through behavioral and histological data capture that their delivery method was equivalent to direct injection of GDNF the current gold standard for delivering this drug in Parkinson disease despite its traumatic nature and high complication rates in diffusing drugs
to the brain. The researchers chose to test their delivery method with GDNF because the therapy has been shown to delay and even reverse disease progression of Parkinson disease in preclinical models.
Nasal mucosal grafting is a technique regularly used in the ENT field to reconstruct the barrier around the brain after surgery to the skull base.
ENT surgeons commonly use endoscopic approaches to remove brain tumors through the nose by making a window through the blood-brain barrier to access the brain.
with the nasal lining protecting the brain from infection just as the blood brain barrier has done. Illustration of a brain.
Drugs used to treat a variety of central nervous system diseases may be administered through the nose and diffused through an implanted mucosal graft (A,
in red) to gain access to the brain. Under normal circumstances, there are multiple layers within the nose that block the access of pharmaceutical agents from getting to the brain including bone and the dura/arachnoid membrane
which represents part of the blood-brain barrier (B). After endoscopic skull base surgery (C), all of these layers are removed
and replaced with a nasal mucosal graft, which is 1, 000 times more porous than the native blood-brain barrier.
Consequently, these grafts may be used to deliver very large drugs, including proteins, which would otherwise be blocked by the blood-brain barrier.
Garyfallia Pagonis and Benjamin S. Bleier, M d. Dr. Bleier saw an opportunity to apply these techniques to the widespread clinical dilemma of delivering drugs across the barrier to the brain and central nervous system.
surgeons may create a creen doorto allow for drug delivery to the brain and central nervous system. The technique has the potential to benefit a large population of patients with neurodegenerative disorders,
where there remains a specific unmet need for blood-brain penetrating therapeutic delivery strategies. e see this expanding beyond Parkinson disease,
as there are multiple diseases of the brain that do not have good therapeutic options, Dr. Bleier said. t is a platform that opens doors for new discovery
#Step Closer to Prosthetic Limbs That Recreate Sense of touch A new study led by neuroscientists from the University of Chicago brings us one step closer to building prosthetic limbs for humans that re-create a sense of touch through a direct interface with the brain.
and what tools are at our disposal to create artificial sensations by stimulating the brain.
had implanted electrodes into the area of the brain that processes touch information from the hand.
Bensmaia and his colleagues have provided the otesscientists can play to produce the usicof the sense of touch in the brain. hen you grasp an object, for example,
However, Bensmaia research shows that, with electrical stimulation of the brain, Weber Law does not applyhe JND remains nearly constant,
no matter the size of the stimulus. This means that the brain responds to electrical stimulation in a much more repeatable,
consistent way than through natural stimulation. t shows that there is something fundamentally different about the way the brain responds to electrical stimulation than it does to natural stimulation,
which links to the device. ogstar products are based on the latest canine neuroscience. Translating the position of the tail
#ipstickin the brain could predict damage just in time A dipstick inserted into the brain can check its energy levels,
according to some neuroscientists. he goal is to save brain tissue, says Elham Rostami of the Karolinska Institute in Stockholm, Sweden.
Last month, Rostami and 47 others published guidelines about how and when to use the technique, known as brain microdialysis,
1-centimetre-long probe directly into the brain. It measures levels of chemicals in the fluid that bathes brain cells
including glucose, the brain main energy source. When used to monitor the brains of people in intensive care after a stroke or head injury,
it warns doctors if glucose starts to dip which can cause brain damage. The probe can theoretically monitor almost any molecule,
but Rostami says the most useful parameters are glucose, which shows if there is a good blood supply,
if brain cells are using the glucose to release energy. Although widely available, the device has so far mainly been used as a research tool rather than to guide treatment.
The woman was in intensive care after a stroke involving bleeding on the surface of her brain.
the woman brain glucose levels had fallen, probably caused by other blood vessels constricting. In response, Rostami team administered a drug to boost her heart rate
and send more blood to the brain. The probe then showed glucose levels beginning to rise,
then pressing the 0. 6mm-diameter probe into the brain tissue. It may seem drastic, but for seriously ill people it might provide vital clues for spotting that their brain is about to suffer damage.
People in intensive care are hooked already up to a host of monitors, which together keep track of numerous parameters including heart rate and levels of glucose and oxygen in the blood.
An electroencephalogram (EEG) can give a read-out of the brain electrical activity, while various kinds of scan can give a snapshot of its health,
what going on in the brain after injury is a good thing, says Karim Brohi a trauma specialist at the Royal London Hospital.
or damage to brain tissue, to Rostami knowledge, but to minimise potential problems it is placed generally on the right side of the brain.
That because the left hemisphere is usually more important for language. The left brain also controls the right side of the body,
#ipstickin the brain could predict damage just in time TO CHECK a car oil levels, use a dipstick.
To check the brain has enough energy, we might be able to do the same, using a probe that can monitor fluid in the brain. he goal is to save brain tissue,
says Elham Rostami of the Karolinska Institute in Stockholm, Sweden. Last month, Rostami and 47 others published guidelines on how and when to use the technique, known as brain microdialysis,
in the hope that more hospitals would adopt it. The approach involves inserting a 1-centimetre-long probe directly into the brain.
It measures levels of chemicals in the fluid that bathes cells including glucose, the brain main energy source.
When used on people in intensive care after a stroke or head injury, it warns doctors
The woman was in intensive care after a stroke that involved bleeding on the surface of her brain.
the woman brain glucose levels were falling, probably because other blood vessels had constricted. In response, Rostami team administered a drug to boost her heart rate
and send more blood to the brain. The probe then showed glucose levels beginning to rise,
It may seem drastic to drill a hole in the skull and press a probe directly into brain tissue,
but for seriously ill people it might provide vital clues that their brain is about to suffer damage.
An electroencephalogram (EEG) can give a read-out of the brain electrical activity, while various kinds of scan can give a snapshot of its health,
what going on in the brain after injury is a good thing, says Karim Brohi, a trauma specialist at the Royal London Hospital.
or damage to brain tissue, to Rostami knowledge, but to minimise potential problems it is placed generally on the right side of the brain.
That because most people are right-handed and the left side of the brain controls the right side of the body,
as well as usually being more important for language r
#Pumping CO2 into frack wells could prevent water contamination Sometimes two problems can cancel each other out.
and use a few hundred watts, says Wilfred van der Wiel of the University of Twente in The netherlands. he human brain can do orders of magnitude more and uses only 10 to 20 watts.
then they are operating in parallel much like neurons in the human brain, which is especially good at such tasks.
and use a few hundred watts, says Wilfred van der Wiel of the University of Twente in The netherlands. he human brain can do orders of magnitude more and uses only 10 to 20 watts.
That because the gold grains work in parallel much like neurons in the human brain which is especially good at these tasks c
and made a replica of a colleague brain in the soft, tissue-like consistency of hydrogel to test it out.
so they based the brain on detailed images of the professor grey matter. e could foresee a future in which, before brain surgery,
the surgeon 3d prints a brain out of hydrogel and then practises on it, says Angelini. hen the surgeon knows exactly how that surgery is going to happen. heye made,
#Earthquake algorithm picks up the brain vibrations Your brain is buzzing. Analysing those natural vibrations might help spot tumours and other abnormalities,
for example, can show up cirrhosis. It is more difficult to measure the elasticity of the brain.
Doctors are limited to touching the brain directly when a section of the skull has been removed during surgery. octors can only feel a few centimetres deep,
so only have information about the elasticity of the surface of the brain, says Stefan Catheline at INSERM in Paris, France.
and others around the world, have been working on a way to use modified MRI SCANNERS to measure brain elasticity.
why not simply take advantage of the brain natural vibrations? e tend to think of the brain as a static organ,
but there is a lot of movement, he says. hen blood is pumped into the brain it pulsates, and induces vibrations.
The idea came to Catheline after he spent time working with seismologists, who study how to extract information from the seismic waves created by earthquakes.
As a result, his team were able to measure the natural vibrations in the brains of two healthy volunteers information normally dismissed as oise The body noise t is an intriguing approach
what going on in the brain than traditional MRI scans, says Neil Roberts at the University of Edinburgh, UK.
So while a bit of brain tissue might look like it made up of identical cells on an MRI
hardness or gloopiness. eing able to essentially touch inside the brain is going to be much more discriminatory than conventional MRI,
for example, have more elasticity than normal brain tissue the new technique might be able to detect those differences.
#Migraines triggered by protein deep in the brain It can start with flashing lights, a tingling sensation and a feeling of unease, followed by excruciating pain.
Now researchers have found that a migraine may be triggered by a protein deep in the brain that stimulates the neurons controlling facial sensations.
and adds weight to the theory that neurons, not blood vessels, are responsible for migraine attacks. here a migraine starts is a key question,
studied two neuropeptides released by neurons thought to play a role in the pain associated with migraine.
These protein-like molecules, called VIP and PACAP, first raised suspicion after they were found to be elevated in blood drained from the brains of people having a migraine attack.
In fact, the only drugs specifically developed for migraine that are in use today triptans were designed to shrink blood vessels in the brain.
and PACAP on a set of neurons that innervate the head and face, which are known to trigger a headache.
The pair measured the electrical activity of these neurons in anaesthetised rats and studied blood vessels in the rodentsbrain to identify
Only PACAP caused the neurons to increase their activity about an hour and a half after it was administered.
but when they were injected directly into the brain, the neurons responsible for a headache no longer surged with activity. hese receptors could genuinely represent a new therapeutic target for migraine,
says Akerman. t appears that these receptors are indeed important, and this is definitely vital to helping us understand migraine
the widening of blood vessels did not happen at the same time as the overactivity of neurons. In other words, the dilation of blood vessels doesn seem to have anything to do with migraine.
Although triptans are prescribed as vasoconstrictors drugs that shrink blood vessels other research suggests that they also block the release of peptides like PACAP from neurons.
#Old rat brains rejuvenated and new neurons grown by asthma drug IT as good as new. An asthma drug has rejuvenated rat brains,
making old rats perform as well as young ones in tests of memory and cognition. Our brains slowly degenerate as we age.
Typically, we lose the ability to make new neurons. And age-related inflammation of the brain is implicated in many brain disorders.
To tackle both problems in one go, Ludwig Aigner at Paracelsus Medical University Salzburg in Austria and his colleagues targeted a set of receptors in the brain that, when activated,
trigger inflammation. These receptors are thought also to be involved in the birth of neurons. A drug called montelukast (Singulair), regularly prescribed for asthma and allergic rhinitis, blocks these receptors,
so Aigner and his colleagues tested it on young and old rats. The team used oral doses equivalent to those taken by people with asthma.
The older animals were 20 months old perhaps between 65 and 75 in human years.
The younger rats were 4 months old roughly the equivalent of 17 human years. The animals were fed the drug daily for six weeks,
He presented his findings earlier this month at the Neuroscience 2015 meeting in Chicago. Old rats that had been given montelukast had 80 per cent less brain inflammation than old rats that hadn been given the drug.
They also had greater new neuron growth than untreated old rats about 50 per cent of that seen in young rats,
says Aigner. The team also found that the blood-brain barrier which stops infectious agents reaching the brain
but weakens with age was treated stronger in old rats. tructurally, the brain had rejuvenated, says Aigner.
The drug had no effect on young animals, probably because it targets inflammation associated with age,
and degenerated brain, he says. think the drug reverses the damage associated with ageing. Because montelukast is used widely
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