The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance1,2. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.
Central nervous system
World Health Organization 2021 Classification of Central Nervous System Tumors and Implications for Therapy for Adult-Type Gliomas
Abstract
Importance Previous histologic classifications of brain tumors have been limited by discrepancies in diagnoses reported by neuropathologists and variability in outcomes and response to therapies. Such diagnostic discrepancies have impaired clinicians’ ability to select the most appropriate therapies for patients and have allowed heterogeneous populations of patients to be enrolled in clinical trials, hindering the development of more effective therapies. In adult-type diffuse gliomas, histologic classification has a particularly important effect on clinical care.
Observations In 2021, the World Health Organization published the fifth edition of the Classification of Tumors of the Central Nervous System. This classification incorporates advances in understanding the molecular pathogenesis of brain tumors with histopathology in order to group tumors into more biologically and molecularly defined entities. As such, tumor classification is significantly improved through better characterized natural histories. These changes have particularly important implications for gliomas. For the first time, adult- and pediatric-type gliomas are classified separately on the basis of differences in molecular pathogenesis and prognosis. Furthermore, the previous broad category of adult-type diffuse gliomas has been consolidated into 3 types: astrocytoma, isocitrate dehydrogenase (IDH) mutant; oligodendroglioma, IDH mutant and 1p/19q codeleted; and glioblastoma, IDH wild type. These major changes are driven by IDH mutation status and include the restriction of the diagnosis of glioblastoma to tumors that are IDH wild type; the reclassification of tumors previously diagnosed as IDH-mutated glioblastomas as astrocytomas IDH mutated, grade 4; and the requirement for the presence of IDH mutations to classify tumors as astrocytomas or oligodendrogliomas.
Conclusions and Relevance The 2021 World Health Organization central nervous system tumor classification is a major advance toward improving the diagnosis of brain tumors. It will provide clinicians with more accurate guidance on prognosis and optimal therapy for patients and ensure that more homogenous patient populations are enrolled in clinical trials, potentially facilitating the development of more effective therapies.
Source: JAMA
Multiple sclerosis: Cholesterol crystals prevent regeneration in central nervous system
Are you like Isaac Newton or Queen Victoria? Analyse your handwriting to find out
Your handwriting can reveal your personality traits, as it comes through the central nervous system, says a new study.
The slant in your handwriting indicates your social stance.
Your handwriting can tell if you have a personality similar to Isaac Newton or Queen Victoria, say scientists who have decoded character traits of some of Britain’s most famous names by decoding their writing style. Researchers from Royal Mail in the UK along with Tracey Trussell, a leading handwriting analyst studied letters and notes from UK’s defining figures such as Rosalind Franklin, Isaac Newton, Queen Victoria, Florence Nightingale, Millicent Fawcett, Charles Darwin and Elizabeth Fry.
The subjects were chosen as they were all keen letter writers and appeared in the 100 Greatest Britons or 100 Great Black Britons lists. “Handwriting is like ‘brain writing’ because it comes through the central nervous system. It’s a snapshot in time,” said Tracey Trussell, handwriting analyst in the UK.
Slant is an emotional barometer that measures people’s social stance. A marked right slant such as that in the writing style of Queen Victoria and Issac Newton indicates that a person is enthusiastic, responsive and that they do not want to hold back and tend to be highly proactive.
Writing consists of three zones — upper, middle and lower. The upper zone focuses on the parts of the letters that extend up wards like b, d, f, h and k, researchers said. People with a large and dominant upper zone have rich imaginations, creative mindsets and big aspirations. They are also intellectually savvy, ethical and have high standards, like Claudia Jones, Ignatius Sancho and Charles Darwin, researchers said.
A person with long and high t-bars is a take-charge sort of person, like Queen Victoria and feminist leader Millicent Fawcett. They are decision makers and perfectionists, they said. Narrow or non-existent right margin is when the end of a sentence leaves no space on the right hand side of the page. Words appear to fall off the edge of the page or dip down like in the cases of Isaac Newton and Charles Darwin. The size of the right hand margin shows the writer’s real feelings towards the future. Those that leave no right margin are outgoing and engaging. They are also impulsive, goal-orientated and driven, researchers said.
A noticeably large (or inflated) letter ‘k’ shows people who are resourceful and defiant like Charles Darwin, Ignatius Sancho and Claudia Jones. They like to get their own way and follow their own path in life, researchers said. “It is amazing to think that something we do every day can reveal so much about us,” said David Gold from Royal Mail — a postal and delivery provider service.
Fabric softener is the #1 cause of indoor air pollution.
Fabric softener ads often portray an image of comfort, freshness and sweetness. Yet most fabric softeners contain a grim list of known toxins which can enter your body through the skin and by inhalation, causing a wide range of health problems, particularly for young children.
Here are some of the harmful ingredients commonly found in liquid or sheet fabric softeners include:
• Chloroform: This substance was used as an anesthesia in the 1800s up through the early 1900s when its potential for causing fatal cardiac arrhythmia was discovered. A carcinogenic neurotoxin, it is on the EPA’s Hazardous Waste list. Inhaling its vapors may cause loss of consciousness, nausea, headache, vomiting, and/or dizziness, drowsiness. It may aggravate disorders of the heart, kidneys or liver. Its effects worsen when subjected to heat.
• A-Terpineol: Causes Central Nervous System (CNS) disorders, meaning problems relating to the brain and spine such as Alzheimer’s disease, ADD, dementia, Multiple Sclerosis, Parkinson’s disease, seizures, strokes, and Sudden Infant Death Syndrome. Early symptoms of CNS problems include aphasia, blurred vision, disorientation, dizziness, headaches, hunger, memory loss, numbness in face, pain in neck and spine. A-Terpineol also irritates the mucous membranes and, if aspirated into the lungs, can cause respiratory depression, pneumonia or fatal edema.
• Benzyl Alcohol: This upper respiratory tract irritant can cause central nervous system (CNS) disorders, headache, nausea, vomiting, dizziness and dramatic drops in blood pressure.
• Benzyl Acetate: This substances has been linked to pancreatic cancer. Its vapors can be irritating to eyes and respiratory passages and it can also be absorbed through the skin.
• Ethanol: Another fabric softener ingredient which is on the EPA’s Hazardous Waste list and linked to CNS disorders.
• Pentane: A chemical known to be harmful if inhaled.
• Ethyl Acetate: This substance, which is on the EPA’s Hazardous Waste list, can be irritating to the eyes and respiratory tract. It may also cause severe headaches and loss of consciousness, as well as damage to the liver and kidneys.
• Camphor: Another substance on the EPA’s Hazardous Waste list. It is easily absorbed through body tissue, causing irritation of eyes, nose and throat. Camphor can also cause dizziness, confusion, nausea, twitching muscles and convulsions.
• Linalool: A narcotic known to cause respiratory problems and CNS disorders. In animal testing, exposure to linalool has resulted in death.
• Phthalates: Used in scented products to help the scent last longer, phthlates have been linked to breast cancer and reproductive system problems.
• Limonene: This known carcinogen can cause irritation to eyes and skin.
• Also, if you follow a vegan lifestyle, you should be aware that many fabric softener sheets are made using tallow, a form of animal fat.
Manufacturers are aware that the products contain toxic chemicals. The packaging on many brands include a warning that the product should not be used on children’s sleepwear. Since some of the same brands also have large images of children and toys, however, consumers may miss the small print message.
Making your own fabric softener is very easy and cost effective . Additionally, using homemade cleaning products helps keep harmful chemicals away. Vinegar is cheap and nontoxic. It naturally removes soap residue, and helps with static reduction during drying. Vinegar contains small amounts of sodium and potassium, which help soften hard water. Homemade fabric softener ingredients are combined with water to make a solution you can store in a container and use each time you do the wash.
Natural Homemade Fabric Softener
Ingredients
- 1 gallon white vinegar
- 30 drops of essential oil (where to buy 100% pure essential oils)
Mix ingredients together and pour into a storage container.
A study of pyrazines in cigarettes and how additives might be used to enhance tobacco addiction
Abstract
Background Nicotine is known as the drug that is responsible for the addicted behaviour of tobacco users, but it has poor reinforcing effects when administered alone. Tobacco product design features enhance abuse liability by (A) optimising the dynamic delivery of nicotine to central nervous system receptors, and affecting smokers’ withdrawal symptoms, mood and behaviour; and (B) effecting conditioned learning, through sensory cues, including aroma, touch and visual stimulation, to create perceptions of pending nicotine reward. This study examines the use of additives called ‘pyrazines’, which may enhance abuse potential, their introduction in ‘lights’ and subsequently in the highly market successful Marlboro Lights (Gold) cigarettes and eventually many major brands.
Methods We conducted internal tobacco industry research using online databases in conjunction with published scientific literature research, based on an iterative feedback process.
Results Tobacco manufacturers developed the use of a range of compounds, including pyrazines, in order to enhance ‘light’ cigarette products’ acceptance and sales. Pyrazines with chemosensory and pharmacological effects were incorporated in the first ‘full-flavour, low-tar’ product achieving high market success. Such additives may enhance dependence by helping to optimise nicotine delivery and dosing and through cueing and learned behaviour.
Conclusions Cigarette additives and ingredients with chemosensory effects that promote addiction by acting synergistically with nicotine, increasing product appeal, easing smoking initiation, discouraging cessation or promoting relapse should be regulated by the US Food and Drug Administration. Current models of tobacco abuse liability could be revised to include more explicit roles with regard to non-nicotine constituents that enhance abuse potential.
IN SEARCH OF THE ORIGIN OF OUR BRAIN
While searching for the origin of our brain, biologists at Heidelberg University have gained new insights into the evolution of the central nervous system (CNS) and its highly developed biological structures. The researchers analysed neurogenesis at the molecular level in the model organism Nematostella vectensis. Using certain genes and signal factors, the team led by Prof. Dr. Thomas Holstein of the Centre for Organismal Studies demonstrated how the origin of nerve cell centralisation can be traced back to the diffuse nerve net of simple and original lower animals like the sea anemone. The results of their research will be published in the journal “Nature Communications”.
Like corals and jellyfish, the sea anemone – Nematostella vectensis – is a member of the Cnidaria family, which is over 700 million years old. It has a simple sack-like body, with no skeleton and just one body orifice. The nervous system of this original multicellular animal is organised in an elementary nerve net that is already capable of simple behaviour patterns. Researchers previously assumed that this net did not evidence centralisation, that is, no local concentration of nerve cells. In the course of their research, however, the scientists discovered that the nerve net of the embryonic sea anemone is formed by a set of neuronal genes and signal factors that are also found in vertebrates.
According to Prof. Holstein, the origin of the first nerve cells depends on the Wnt signal pathway, named for its signal protein, Wnt. It plays a pivotal role in the orderly evolution of different types of animal cells. The Heidelberg researchers also uncovered an initial indication that another signal path is active in the neurogenesis of sea anemones – the BMP pathway, which is instrumental for the centralisation of nerve cells in vertebrates.
Named after the BMP signal protein, this pathway controls the evolution of variouscell types depending on the protein concentration, similar to the Wnt pathway, but in a different direction. The BMP pathway runs at a right angle to the Wnt pathway, thereby creating an asymmetrical pattern of neuronal cell types in the widely diffuse neuronal net of the sea anemone. “This can be considered as the birth of centralisation of the neuronal network on the path to the complex brains of vertebrates,” underscores Prof. Holstein.
While the Wnt signal path triggers the formation of the primary body axis of all animals, from sponges to vertebrates, the BMP signal pathway is also involved in the formation of the secondary body axis (back and abdomen) in advanced vertebrates. “Our research results indicate that the origin of a central nervous system is closely linked to the evolution of the body axes,” explains Prof. Holstein.
Antidepressant Drugs Affect Neurotransmitters Differently, Sometimes Increasing Thoughts Of Suicide Among Young Adults
The idea it gets worse before it gets better is applicable to certain antidepressants, according to a new paper published in the journal Trends in Cognitive Sciences.
Selective serotonin reuptake inhibitors (SSRIs) are among the most prescribed drugs (or overprescribed depending on who you talk to) for psychiatric disorders, including depression, anxiety, and eating disorders. They work to increase the brain’s level of serotonin — a chemical that work as a neurotransmitter and is responsible for maintaining mood balance — while inhibiting its reuptake (absorption) into the brain’s presynaptic cell. Chemical synapses are what allow neurons to form circuits within the central nervous system, as well as help connect to and control other systems of the body.
While serotonin can increase up to hours after an SSRI is taken, it takes two weeks before patients notice a subside in symptoms. It’s during this delay researchers from Otto-von-Guericke University believe depression gets worse before it gets better. Specifically, this delay stems from the different ways SSRI affects serotonin and another brain chemical called glutamate, which are both released from the serotonin neuron. Glutamate is the brain’s main excitatory neurotransmitter, and it’s important for neural communication, memory formation, learning and regulation.
Researchers culled data from existing studies and found when taking an SSRI, serotonin is immediately amplified while glutamate is suppressed. This balance is only restored after several days of drug treatment, Adrian Fischer, lead study author, said in a press release. Fischer added the serotonin component has been linked to motivation, while the glutamate component has been linked to pleasure and learning.
Put it another way: An SSRI immediately boosts motivation in depressed patients, while at the same time it’s hampering hedonic components (pleasure) of the reward system. The answer isn’t a higher dose of SSRIs either. Instead, researchers found this combination, whatever the dose, “could lead to the facilitation of suicidal thoughts or behavior in the early weeks of SSRI administration,” especially in young adults.
Pharmacology experts refer to this as a “paradoxical reaction.” Medical Daily previously reported this type of reaction is not uncommon among depression sufferers. One study was on par with the current study’s findings: 42 10- to 17-year-olds were compelled to self-harm after taking Prozac, four of which were hospitalized.
Fischer and his team concluded their paper “offers a framework of directly testable predictions for a better understanding and interpretation of studies employing SSRI challenges.” It also opens potentials for new drugs aiming to delay onset of SSRIs in depression. As always, consult with your doctor on the medication that is best suited for your particular symptoms; antidepressant, and otherwise prescription drugs, aren’t one size fits all. And if patients are prescribed medication, be sure to read up on possible side effects.
Source: Fischer A, Jocham G, Ullsperger M. Dual serotonergic signals: a key to understanding paradoxical effects? Trends in Cognitive Sciences. 2014.
Brain Clears Toxins During Sleep.
Scientists have long wondered why sleep is restorative and why lack of sleep impairs brain function.
Now, new animal research suggests how the sleep state may help clear the body of potentially toxic central nervous system (CNS) metabolites.
Proteins linked to neurodegenerative diseases, including β-amyloid (Aβ), are present in the interstitial space surrounding cells in the brain. In a series of experiments, researchers tested the hypothesis that Aβ clearance is increased during sleep and that the sleep-wake cycle regulates the glial cell–dependent glymphatic system, which is responsible for clearing waste from the brain and spinal cord.
“Basically, we found a new function of sleep,” said study lead author Lulu Xie, PhD, Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, New York.
“When mice are awake, the brain cells continuously produce toxic waste. This waste can build up in the spaces between the brain cells and damage them. However, during sleep, the spaces between brain cells increase, which may help the brain flush out the toxic waste. Therefore, a good sleep can clear the brain.”
“Sleep changes the cellular structure of the brain. It appears to be a completely different state,” Maiken Nedergaard, MD, DMSc, codirector of the Center for Translational Neuromedicine at the University of Rochester Medical Center, who is a leader of the study, said in a statement from the National Institute of Neurological Disorders and Stroke, which supported the study.
The new research was published October 18 in Science.
Sleeping vs Awake Brain
The researchers infused fluorescent dye into the cerebrospinal fluid (CSF) of mice and observed it flow through the brain. At the same time, they monitored electrical brain activity and wakefulness with electrocorticography (EcoG) and electromyography (EMG)..
“In the sleeping brain, we found the CSF flushed into the brain very quickly and broadly,” said Dr. Xie. “After half an hour, we woke the mice up by gently touching their tails, and injected another color of dye. But what we saw is that CSF barely flowed when the same mice were awake.”
These results suggest that the awake brain may have more resistance to CSF influx, which leads to the assumption that the path of CSF flow into the brain is smaller in the awake brain, said Dr. Xie.
Next, the scientists inserted electrodes into the brain to directly measure the space between brain cells, and found that it increased by around 60% when the mice were asleep.
“Theoretically, big spaces lead to easier fluid influx,” said Dr. Xie. “So we presumed that the clearance of the toxic protein between cells will become more efficient.”
To test this assumption, they infused radio-labeled Aβ into the brain and measured how long it stayed in both the sleeping brain and the awake brain.
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We found Aβ disappeared 2-fold faster in the sleeping mice brains as compared with awake mice,” noted Dr. Xie. “Based on this experiment, we can see that the sleeping brain is more capable of clearing out the toxic protein.”
Technically, it might be relatively easy to study these processes in humans, possibly using magnetic resonance imaging. However, Dr. Xie said she does not know when human trials, which involve “a lot more concerns” than animal experiments, might come about.
“These results may have broad implications for multiple neurological disorders,” said Jim Koenig, PhD, a program director at the National Institute of Neurological Disorders and Stroke (NINDS), which funded the study, in a statement. “This means the cells regulating the glymphatic system may be new targets for treating a range of disorders.”
Scientists identify clue to regrowing nerve cells.
Researchers atWashington University School of Medicine in St. Louis have identified a chain reaction that triggers the regrowth of some damaged nerve cell branches, a discovery that one day may help improve treatments for nerve injuries that can cause loss of sensation or paralysis.
The scientists also showed that nerve cells in the brain and spinal cord are missing a link in this chain reaction. The link, a protein called HDAC5, may help explain why these cells are unlikely to regrow lost branches on their own. The new research suggests that activating HDAC5 in the central nervous system may turn on regeneration of nerve cell branches in this region, where injuries often cause lasting paralysis.
“We knew several genes that contribute to the regrowth of these nerve cell branches, which are called axons, but until now we didn’t know what activated the expression of these genes and, hence, the repair process,” said senior author Valeria Cavalli, PhD, assistant professor of neurobiology. “This puts us a step closer to one day being able to develop treatments that enhance axon regrowth.”
The research appears Nov. 7 in the journal Cell.
Axons are the branches of nerve cells that send messages. They typically are much longer and more vulnerable to injury than dendrites, the branches that receive messages.
In the peripheral nervous system — the network of nerve cells outside the brain and spinal column — cells sometimes naturally regenerate damaged axons. But in the central nervous system, comprised of the brain and spinal cord, injured nerve cells typically do not replace lost axons.
Working with peripheral nervous system cells grown in the laboratory, Yongcheol Cho, PhD, a postdoctoral research associate in Cavalli’s laboratory, severed the cells’ axons. He and his colleagues learned that this causes a surge of calcium to travel backward along the axon to the body of the cell. The surge is the first step in a series of reactions that activate axon repair mechanisms.
In peripheral nerve cells, one of the most important steps in this chain reaction is the release of a protein, HDAC5, from the cell nucleus, the central compartment where DNA is kept. The researchers learned that after leaving the nucleus, HDAC5 turns on a number of genes involved in the regrowth process. HDAC5 also travels to the site of the injury to assist in the creation of microtubules, rigid tubes that act as support structures for the cell and help establish the structure of the replacement axon.
When the researchers genetically modified the HDAC5 gene to keep its protein trapped in the nuclei of peripheral nerve cells, axons did not regenerate in cell cultures. The scientists also showed they could encourage axon regrowth in cell cultures and in animals by dosing the cells with drugs that made it easier for HDAC5 to leave the nucleus.
When the scientists looked for the same chain reaction in central nervous system cells, they found that HDAC5 never left the nuclei of the cells and did not travel to the site of the injury. They believe that failure to get this essential player out of the nucleus may be one of the most important reasons why central nervous system cells do not regenerate axons.
“This gives us the hope that if we can find ways to manipulate this system in brain and spinal cord neurons, we can help the cells of the central nervous system regrow lost branches,” Cavalli said. “We’re working on that now.”
Cavalli also is collaborating with Susan Mackinnon, MD, the Sydney M. Shoenberg Jr. and Robert H. Shoenberg Professor of Surgery, chief of the Division of Plastic and Reconstructive Surgery and a pioneer in peripheral nerve transplants. The two are investigating whether HDAC5 or other components of the chain reaction can be used to help restore sensory functions in nerve grafts.
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