Posts tagged science

A new study from Karolinska Institutet shows that a part of the nervous system, the parasympathetic nervous system, is formed in a way that is different from what researchers previously believed. In this study, which is published in the journal Science, a new phenomenon is investigated within the field of developmental biology, and the findings may lead to new medical treatments for congenital disorders of the nervous system.

Almost all of the body’s functions are controlled by the autonomous, involuntary nervous system, for example the heart and blood vessels, liver and gastrointestinal system. At rest, the body is set up for energy saving functions, which is regulated by the parasympathetic part of the autonomous nervous system.

Current understanding is that many important types of cells, including the parasympathetic nerve cells in various organs, originate in early progenitor cells that move short distances while the embryo is still small. But this model does not explain how many of our organs – which develop relatively late, when the embryo is large – are furnished with cells that form the parasympathetic neurons.

This study alters a fundamental principal of our understanding of how the peripheral nervous system develops in the body. Researchers at Karolinska Institutet have made three-dimensional reconstructions of mouse embryos. These show that the parasympathetic neurons are formed from immature glial cells known as Schwann cell precursors that travel along the peripheral nerves out to the body’s tissues and organs. The immature cells have the properties of stem cells and may be the origin of several different types of cells. For example, the researchers behind this new study have previously demonstrated that the majority of our melanocytes (pigment cells) are born from these cells.

New principal of developmental biology

"Our study focuses on a new principal of developmental biology, a targeted recruitment of cells that are probably also used in the reconstruction of tissue. Despite the elegance, simplicity and beauty of this principal, it is still unclear how the number of parasympathetic neurons is controlled and why only some of the cells transported by nerves are transformed into that which becomes an important part of the nervous system", says Igor Adameyko at the Department of Physiology and Pharmacology who, together with Patrik Ernfors at the Department of Medical Biochemistry and Biophysics, is responsible for the study.

Somewhat surprisingly, the researchers found that the entire parasympathetic nervous system arises from these progenitor cells that travel along the peripheral nerves. The researchers hope that this discovery will open up the possibility of new ways to treat congenital disorders of the autonomous nervous system using regenerative medicine.

(Source: ki.se)

In a new study published online in the Journal of the American Heart Association June 12, 2014, researchers at Columbia Engineering report that they have identified a new component of the biological mechanism that controls blood flow in the brain. Led by Elizabeth M. C. Hillman, associate professor of biomedical engineering, the team has demonstrated, for the first time, that the vascular endothelium plays a critical role in the regulation of blood flow in response to stimulation in the living brain.

(Image caption: In-vivo two-photon microscopy image of endothelial cells lining surface arteries in the brain (green, TIE-2/GFP). Red cells are astrocytes labeled with sulphorhodamine. New results suggest that the continuous pathway of endothelial cells within the brain’s arteries is essential for propagating signals that orchestrate local dilation and increases in blood flow in response to local neuronal activity. Credit: Image courtesy of Elizabeth Hillman)

“We think we’ve found a missing link in our understanding of how the brain dynamically tunes its blood flow to stay in sync with the activity of neurons,” says Hillman, who has a joint appointment in Radiology. She is also a member of the Zuckerman Mind Brain Behavior Institute and the Kavli Institute for Brain Science at Columbia. Hillman has spent more than 10 years using advanced imaging tools to study how blood flow is controlled in the brain. “Earlier studies identified small pieces of the puzzle, but we didn’t believe they formed a cohesive ‘big picture’ that unified everybody’s observations. Our new finding seems to really connect the dots.”

Understanding how and why the brain regulates its blood flow could provide important clues to understanding early brain development, disease, and aging. The brain increases local blood flow when neurons fire, and this increase is what is detected by a functional magnetic resonance imaging (fMRI) scan. Hillman found that the vascular endothelium, the inner layer of blood vessels, plays a critical role in propagating and shaping the blood flow response to local neuronal activity. While the vascular endothelium is known to do this in other areas of the body, until now the brain was thought to use a different, more specialized mechanism and researchers in the field were focused on the cells surrounding the vessels in the brain.

“Once we realized the importance of endothelial signaling in the regulation of blood flow in the brain,” Hillman adds, “we wondered whether overlooking the vascular endothelium might have led researchers to misinterpret their results.”

“As we identified this pathway, so many things fell into place,” she continues, “We really hope that our work will encourage others to take a closer look at the vascular endothelium in the brain. So far, we think that our findings have far-reaching and really exciting implications for neuroscience, neurology, cardiovascular medicine, radiology, and our overall understanding of how the brain works.” 

This research was carried out in Hillman’s Laboratory for Functional Optical Imaging, led by PhD student and lead author on the study, Brenda Chen. Other lab members who assisted with the study included PhD and MD/PhD students from Columbia Engineering, Neurobiology and Behavior, and Columbia University Medical Center. The group combined their engineering skills with their expertise in neuroscience, biology, and medicine to understand this new aspect of brain physiology.

To tease apart the role of endothelial signaling in the living brain, they had to develop new ways to both image the brain at very high speeds, and also to selectively alter the ability of endothelial cells to propagate signals within intact vessels. The team achieved this through a range of techniques that use light and optics, including imaging using a high-speed camera with synchronized, strobed LED illumination to capture changes in the color, and thus the oxygenation level of flowing blood. Focused laser light was used in combination with a fluorescent dye within the bloodstream to cause oxidative damage to the inner endothelial layer of blood brain arterioles, while leaving the rest of the vessel intact and responsive. The team showed that, after damaging a small section of a vessel using their laser, the vessel no longer dilated beyond the damaged point. When the endothelium of a larger number of vessels was targeted in the same way, the overall blood flow response of the brain to stimulation was significantly decreased.

“Our finding unifies what is known about blood flow regulation in the rest of the body with how it is regulated in the brain,” Hillman explains. “This has wider reaching implications since there are many disease states known to affect blood flow regulation in the rest of the body that, until now, were not expected to directly affect brain health.” For instance, involvement of the endothelium might explain neural deficits in diabetics; a clue that could lead to new diagnostics tests and treatments for neurological conditions associated with broader cardiovascular problems.

“Improving our fundamental understanding of how and why the brain regulates its blood flow is key to understanding how and when this mechanism could be altered or broken,” she says. “We think this could extend to studies of early brain development, aging, and diseases such as Alzheimer’s and dementia.”

The team’s research findings may also explain the effects of some drugs on the brain, and on the fMRI response to stimulation, since the vascular endothelium is exposed to chemicals in the bloodstream. “Overall, this work could dramatically improve our ability to interpret fMRI data collected in humans, perhaps making it a better tool for doctors to understand brain disease,” she adds. Hillman’s work in this area is also featured in an upcoming review in the 2014 edition of the Annual Review of Neuroscience, as well as an article in Scientific American MIND (July/August 2014).

Hillman plans next to address the broad range of implications her latest finding may have. She wants to explore the effects of drugs and disease states on the coupling of blood flow to neuronal activity in the brain, and is now starting studies to explore fMRI data from a range of different disease states to see whether she can find signs of neurovascular dysfunction. She is also working on characterizing the co-evolution of neuronal and hemodynamic activity during brain development and is beginning to develop new imaging tools that will enable non-invasive, inexpensive monitoring of brain hemodynamics in infants and children who cannot be imaged within an MRI scanner.

“Our latest finding gives us a new way of thinking about brain disease—that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels,” Hillman adds. “This gives us a new target to focus on to explore treatments for a wide range of disorders that have, until now, been thought of as impossible to treat. The brain’s vasculature is a critical partner in normal brain function. We hope that we are slowly getting closer to untangling some of the mysteries of the human brain.”

(Source: engineering.columbia.edu)

Fighting off illness- rather than the illness itself- causes sleep deprivation and affects memory, a new study has found.

University of Leicester biologist Dr Eamonn Mallon said a common perception is that if you are sick, you sleep more.

But the study, carried out in flies, found that sickness induced insomnia is quite common.

(Image credit)

The research has been published in the journal PeerJ.

Dr Mallon said: “Think about when you are sick. Your sleep is disturbed and you’re generally not feeling at your sharpest. Previously work has been carried out showing that being infected leads to exactly these behaviours in fruit flies.

“In this paper we show that it can be the immune system itself that can cause these problems. By turning on the immune system in flies artificially (with no infection present) we reduced how long they slept and how well they performed in a memory test.

“This is an interesting result as these connections between the brain and the immune system have come to the fore recently in medicine. It seems to be because the two systems speak the same chemical language and often cross-talk. Having a model of this in the fly, one of the main systems used in genetic research will be a boost to the field.

“The key message of this study is that the immune response, sleep and memory seem to be intimately linked. Medicine is beginning to study these links between the brain and the immune system in humans. Having an easy to use insect model would be very helpful.”

(Source: www2.le.ac.uk)

Traumatic brain injuries from sports, recreational activities, falls or car accidents are the leading cause of death and disability in children and adolescents. While previously it was believed that the window for brain recovery was at most one year after injury, new research from the Center for BrainHealth at The University of Texas at Dallas published online today in the open-access journal Frontiers in Neurology shows cognitive performance can be improved to significant degrees months, and even years, after injury, given targeted brain training.

"The after-effects of concussions and more severe brain injuries can be very different and more detrimental to a developing child or adolescent brain than an adult brain," said Dr. Lori Cook, study author and director of the Center for BrainHealth’s pediatric brain injury programs. "While the brain undergoes spontaneous recovery in the immediate days, weeks, and months following a brain injury, cognitive deficits may continue to evolve months to years after the initial brain insult when the brain is called upon to perform higher-order reasoning and critical thinking tasks."

Twenty adolescents, ages 12-20 who experienced a traumatic brain injury at least six months prior to participating in the research and were demonstrating gist reasoning deficits, or the inability to “get the essence” from dense information, were enrolled in the study. The participants were randomized into two different cognitive training groups – strategy-based gist reasoning training versus fact-based memory training.

Participants completed eight, 45-minute sessions over a one-month period. Researchers compared the effects of the two forms of training on the ability to abstract meaning and recall facts. Testing included pre- and post-training assessments, in which adolescents were asked to read several texts and then craft a high-level summary, drawing upon inferences to transform ideas into novel, generalized statements, and recall important facts.

After training, only the gist-reasoning group showed significant improvement in the ability to abstract meanings – a foundational cognitive skill to everyday life functionality. Additionally, the gist-reasoning-trained group showed significant generalized gains to untrained areas including executive functions of working memory (i.e., holding information in mind for use – such as performing mental addition or subtraction ) and inhibition (i.e., filtering out irrelevant information). The gist-reasoning training group also demonstrated increased memory for facts, even though this skill was not specifically targeted in training.

"These preliminary results are promising in that higher-order cognitive training that focuses on ‘big picture’ thinking improves cognitive performance in ways that matter to everyday life success," said Dr. Cook. "What we found was that training higher-order cognitive skills can have a positive impact on untrained key executive functions as well as lower-level, but also important, processes such as straightforward memory, which is used to remember details. While the study sample was small and a larger trial is needed, the real-life application of this training program is especially important for adolescents who are at a very challenging life-stage when they face major academic and social complexities. These cognitive challenges require reasoning, filtering, focusing, planning, self-regulation, activity management and combating ‘information overload,’ which is one of the chief complaints that teens with concussions express."

This research advances best practices by implicating changes to common treatment schedules for traumatic brain injury and concussion. The ability to achieve cognitive gains through a brain training treatment regimen at chronic stages of brain injury (6 months or longer) supports the need to monitor brain recovery annually and offer treatment when deficits persist or emerge later.

"Brain injuries require routine follow-up monitoring. We need to make sure that optimized brain recovery continues to support later cognitive milestones, and that is especially true in the case of adolescents," said Dr. Sandra Bond Chapman, study author, founder and chief director of the Center for BrainHealth and Dee Wyly Distinguished University Chair at The University of Texas at Dallas. "What’s promising is that no matter the severity of the injury or the amount of time since injury, brain performance improved when teens were taught how to strategically process incoming information in a meaningful way, instead of just focusing on rote memorization."

(Source: brainhealth.utdallas.edu)

How neurons are created and integrate with each other is one of biology’s greatest riddles. Researcher Dietmar Schmucker from VIB-KU Leuven unravels a part of the mystery in Science magazine. He describes a mechanism that explains novel aspects of how the wiring of highly branched neurons in the brain works. These new insights into how complex neural networks are formed are very important for understanding and treating neurological diseases.

Neurons, or nerve cells
It is estimated that a person has 100 billion neurons, or nerve cells. These neurons have thin, elongated, highly branched offshoots called dendrites and axons. They are the body’s information and signal processors. The dendrites receive electrical impulses from the other neurons and conduct these to the cell body. The cell body then decides whether stimuli will or will not be transferred to other cells via the axon.

The brain’s wiring is very complex. Although the molecular mechanisms that explain the linear connection between neurons have already been described numerous times, little is as yet known about how the branched wiring works in the brain.

The connections between nerve cells
Prior research by Dietmar Schmucker and his team lead to the identification of the Dscam1 protein in the fruit fly. The neuron can create many different protein variations, or isoforms, from this same protein. The specific set of isoforms that occurs on a neuron’s cell surface determines the neuron’s unique molecular identity and plays an important role in the establishment of accurate connections. In other words, it describes why certain neurons either come into contact with each other or reject each other.

Recent work by Haihuai He and Yoshiaki Kise from Dietmar’s team indicates that different sets of Dscam1 isoforms occur inside one axon, between the newly formed offshoots amongst each other. If this was not the case, then only linear connections could come about between neurons. These results indicate for the first time the significance of why different sets of the same protein variations can occur in one neuron and it could explain mechanistically how this contributes to the complex wiring in our brain.

Clinical impact
Although this research was done with fruit flies, it also provides new insights that help explain the wiring and complex interactions of the human brain and shine a new light on neurological development disorders such as autism. Thorough knowledge of nerve cell creation and their neural interactions is considered essential knowledge for the future possibility of using stem cell therapy as standard treatment for certain nervous system disorders.

Questions
Given that this research can raise many questions, we would like to refer your questions in your report or article to the email address that the VIB has made available for this purpose. All questions regarding this and other medical research can be directed to: patients@vib.be.

Relevant scientific publication
The above-mentioned research was published in the prominent magazine Science.

(Source: vib.be)

A recently published clinical study in the Journal of the American Medical Association has answered an urgent question that long puzzled ER pediatricians: Is the drug lorazepam really safer and more effective than diazepam – the U.S. Food and Drug Administration-approved medication as first line therapy most often used by emergency room doctors to control major epileptic seizures in children?

The answer to that question – based on a double-blind, randomized clinical trial that compared outcomes in 273 seizure patients, about half of whom were given lorazepam – is a clear-cut “no,” said Prashant V. Mahajan, M.D., M.P.H., M.B.A, one of the authors of the study.

“The results of our clinical trial were very convincing, and they showed clearly that the two medications are just about equally effective and equally safe when it comes to treating status epilepticus [major epileptic brain seizures in children],” Dr. Mahajan said. “This is an important step forward for all of us who frequently treat kids in the ER for [epilepsy-related] seizures, since it answers the question about the best medication to use in ending the convulsions and getting these patients back to normal brain functioning.”

Describing the brain convulsions that were targeted by the study, its authors pointed out that status epilepticus occurs when an epilepsy-related seizure lasts more than 30 minutes. Such seizures – which occur in more than 10,000 U.S. pediatric epilepsy patients every year – can cause permanent brain damage or even death, if allowed to persist.

Published in JAMA, the study, “Lorazepam vs Diazepam for Pediatric Status Epilepticus: A Randomized Clinical Trial,” was designed to test earlier assertions by many clinicians that lorazepam was more effective at controlling pediatric seizures. The study-authors wrote, “Potential advantages proposed in some studies of lorazepam include improved effectiveness in terminating convulsions, longer duration of action compared with diazepam, and lower incidence of respiratory depression. Specific pediatric data comparing diazepam with lorazepam suggest that lorazepam might be superior, but they are limited to reports from single institutions or retrospective studies with small sample sizes, thus limiting generalizability.”

Based on data collected over four years at 11 different U.S. pediatric emergency departments, the new study found that “treatment with lorazepam [among pediatric patients with convulsive status epilepticus] did not result in improved efficacy or safety, compared with diazepam.”

That determination led the study authors to conclude: “These findings do not support the preferential use of lorazepam for this condition.”

Dr. Mahajan, a nationally recognized researcher in pediatric emergency medicine and a Wayne State University School of Medicine pediatrics professor recently appointed chair of the American Academy of Pediatrics Executive Committee of the Section on Emergency Medicine, said the JAMA study provides “a compelling example of how effective research in pediatric medicine, based on treatment of patients right in the clinical setting, can play a major role in improving outcomes.”

Children’s Hospital of Michigan Chief of Pediatrics Steven E. Lipshultz, M.D., said this recent breakthrough will “undoubtedly result in better care for pediatric patients who present in the emergency room with seizures related to epilepsy.

“There’s no doubt that combining excellent research with excellent treatment is the key to achieving the highest-quality outcomes for patients – and Dr. Mahajan’s cutting-edge study is a terrific example of how kids are benefiting from the research that goes on here at Children’s every single day,” said Dr. Lipshultz.

(Source: media.wayne.edu)