Is There a Period of Increased Vulnerability for Repeat Traumatic Brain Injury?

Repeat traumatic brain injury affects a subgroup of the 3.5 million people who suffer head trauma each year. Even a mild repeat TBI that occurs when the brain is still recovering from an initial injury can result in poorer outcomes, especially in children and young adults. A metabolic marker that could serve as the basis for new mild TBI vulnerability guidelines is described in an article in Journal of Neurotrauma, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Journal of Neurotrauma website.

In an Editorial, “The Window of Risk in Repeated Head Injury,” accompanying this article, John T. Povlishock, PhD, Editor-in-Chief of Journal of Neurotrauma and Professor, VCU Neuroscience Center, Medical College of Virginia, Richmond, states that recent studies of TBI in animal models have shown that while repeat injury can exacerbate structural, functional, metabolic, and behavioral responses, “these responses only occur when the injury is repeated within a specific time frame post-injury.”

"Specifically, this window of risk is greatest when the interval between injuries is short, hours to days, while any risk for increased damage is obviated when the intervals between injuries are elongated over days to weeks," says Dr. Povlishock. It is not yet clear if these time periods of increased risk are age- or gender-specific or depend on the intensity of the initial injury.

A consistent finding following TBI in both humans and animal models is a decrease in glucose uptake by the brain. Mayumi Prins, Daya Alexander, Christopher Giza, and David Hovda, The UCLA Brain Injury Research Center, Los Angeles, CA, simulated single and repeat (after 1 or 5 days) mild TBI in rats and measured cerebral glucose metabolism. They tested the hypothesis that the rats’ brains would be more vulnerable to the damaging effects of repeat TBI at 1 day post-injury, when glucose metabolism was still decreased, than at 5 days, when it had returned to normal levels.

In the article, “Repeat Mild Traumatic Brain Injury: Mechanisms of Cerebral Vulnerability,” the authors propose that the duration of metabolic slowdown in the brain could serve as a valuable biomarker for how long a child might be at increased risk of repeat TBI.

Researchers Find Causality in the Eye of the Beholder

We rely on our visual system more heavily than previously thought in determining the causality of events. A team of researchers has shown that, in making judgments about causality, we don’t always need to use cognitive reasoning. In some cases, our visual brain—the brain areas that process what the eyes sense—can make these judgments rapidly and automatically.

The study appears in the latest issue of the journal Current Biology.

“Our study reveals that causality can be computed at an early level in the visual system,” said Martin Rolfs, who conducted much of the research as a post-doctoral fellow in NYU’s Department of Psychology. “This finding ends a long-standing debate over how some visual events are processed: we show that our eyes can quickly make assessments about cause-and-effect—without the help of our cognitive systems.”

Rolfs is currently a research group leader at the Bernstein Center for Computational Neuroscience and the Department of Psychology of Berlin’s Humboldt University. The study’s other co-authors were Michael Dambacher, post-doctoral researcher at the universities of Potsdam and Konstanz, and Patrick Cavanagh, professor at Université Paris Descartes.

We frequently make rapid judgments of causality (“The ball knocked the glass off the table”), animacy (“Look out, that thing is alive!”), or intention (“He meant to help her”). These judgments are complex enough that many believe that substantial cognitive reasoning is required—we need our brains to tell us what our eyes have seen. However, some judgments are so rapid and effortless that they “feel” perceptual – we can make them using only our visual systems, with no thinking required.

It is not yet clear which judgments require significant cognitive processing and which may be mediated solely by our visual system. In the Current Biology study, the researchers investigated one of these—causality judgments—in an effort to better understand the division of labor between visual and cognitive processes.

Potential Drug Target to Block Cell Death in Parkinson’s Disease

Oxidative stress is a primary villain in a host of diseases that range from cancer and heart failure to Alzheimer’s disease, Amyotrophic Lateral Sclerosis and Parkinson’s disease. Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have found that blocking the interaction of a critical enzyme may counteract the destruction of neurons associated with these neurodegenerative diseases, suggesting a potential new target for drug development.

These findings appear in the January 11, 2013 edition of The Journal of Biological Chemistry.

During periods of cellular stress, such as exposure to UV radiation, the number of highly reactive oxygen-containing molecules can increase in cells, resulting in serious damage. However, relatively little is known about the role played in this process by a number of stress-related enzymes.

In the new study, the TSRI team led by Professor Philip LoGrasso focused on an enzyme known as c-jun-N-terminal kinase (JNK). Under stress, JNK migrates to the mitochondria, the part of the cell that generates chemical energy and is involved in cell growth and death. That migration, coupled with JNK activation, is associated with a number of serious health issues, including mitochondrial dysfunction, which has long been known to contribute to neuronal death in Parkinson’s disease. 

The new study showed for the first time that the interaction of JNK with a protein known as Sab is responsible for the initial JNK localization to the mitochondria in neurons. The scientists also found blocking JNK mitochondrial signaling by inhibiting JNK interaction with Sab can protect against neuronal damage in both cell culture and in the brain.

In addition, by treating JNK with a peptide inhibitor derived from a mitochondrial membrane protein, the team was able to induce a two-fold level of protection of neurons in the substantia nigra pars compacta, the brain region devastated by Parkinson’s disease.

The study noted that this inhibition leaves all other cell signaling intact, which could mean potentially fewer side effects in any future therapies.

“This may be a novel way to prevent neuron degeneration,” said LoGrasso. “Now we can try to make compounds that block that translocation and see if they’re therapeutically viable.”

Study: Model for Brain Signaling Flawed

A new study out today in the journal Science turns two decades of understanding about how brain cells communicate on its head. The study demonstrates that the tripartite synapse – a model long accepted by the scientific community and one in which multiple cells collaborate to move signals in the central nervous system – does not exist in the adult brain. 

“Our findings demonstrate that the tripartite synaptic model is incorrect,” said Maiken Nedergaard, M.D., D.M.Sc., lead author of the study and co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine. “This concept does not represent the process for transmitting signals between neurons in the brain beyond the developmental stage.”

The central nervous system is home to many different cells. While neurons tend to garner the most attention, it is only recently that the function of the brain’s other cells have been fully appreciated. Glial cells known as astrocytes, for example, had long been considered mainly the “glue” that helps hold all the other cells in the central nervous system in place. Scientists now understand that that these cells are essential to maintaining a healthy environment in the brain by helping carry out functions such as removing waste.

“Neurons are like a racing car,” said Nedergaard. “While the driver gets all the credit, there are often 20 people behind the scenes that are optimizing his or her success.”

However, when it comes to moving signals between neurons in the brain it turns out that the scientists may have vastly exaggerated the role of the astrocyte.   

Neurons are connected to each other via axons or “arms” that extend from the cell’s main body. Communication between neighboring neurons takes place where axons meet other nerve cells – called a synaptic juncture – when an electrical charge causes chemicals called neurotransmitters or glutamate to be released by one cell and “read” by receptors on the surface of the opposite. The two cells do not actually touch, so the chemicals messages must pass through a gap in the synaptic juncture. The space around this gap is insulated by astrocytes.   

Under the tripartite synapse model, both astrocytes and neurons were believed to play a role in the “conversation” between cells. This understanding was largely based on animal models which showed active receptors and neurotransmission between not only the nerve cells but also the nearby astrocytes.  

Specifically, a key neurotransmission receptor called metabotropic glutamate receptor 5 (mGluR5) was observed to be present and active in astrocytes at the synaptic juncture. It was also observed that when the mGluR5 receptor was activated, the astrocytes would release chemical transmitters that were in turn read by the nerve cells. These findings led to the conclusion that astrocytes must in some manner modulate the signaling process between brain cells. 

While this model has held sway for decades, scientists have long been frustrated by their inability to influence this process by targeting it with drugs.

“If this concept was correct, it should have given rise to a clinical trial by now,” said Nedergaard. “It has not, which tells us that with so many labs work on this for 20 years that there must be something wrong.”

One of the barriers to understanding precise mechanics of passing signals from one neuron to another has been the inability to observe this process in the adult brain. The tripartite synapse model was based – in part – by examining the activity in the brains of very young rodents. Adult rodents could not be similarly studied because the synapses in the brain would die before they could be fully analyzed. This ultimately led to the presumption that the signaling process that was witnessed in the young brain carried over to adulthood. 

Collaborating with researchers at the University of Rochester’s Institute of Optics, Nedergaard and her team developed a new 2-photon microscope that enables researchers to observe glia activity in the living brain. Using both this method and by analyzing the gene and protein expression in the brain the researchers discovered that the mGluR5 largely disappear in the glial cells of adult mice meaning that these cells do not directly respond to synaptic neuronal signalling, thus calling into question the concepts that drive most of ongoing research in the field.

“The process of neuron-glial transmission as conceived by the tripartite synapse model appears to just be a simplistic signaling pathway that ‘teaches’ the synapse how to behave,” said Nedergaard. “Once the brain matures, it goes away.”

Innovative system for the rehabilitation of people with brain damage

The Biomechanics Institute of Valencia (IBV) is currently taking part in the European project WALKX with the aim of developing an innovative rehabilitation system to improve the quality of life of people who have suffered brain damage. This system will allow home rehabilitation and improve patient’s autonomy.

WALKX is a two-year research project for the benefit of small and medium sized enterprises (SMEs), co-funded by the European Commission through the Seventh Framework Programme.

The user friendly walking training device the partners are designing will support the patient in raising from sitting to standing position and enable the patient to perform walking training and improve his/her manoeuvrability. “An upper body stabilizing and controllable supporting vest will be developed. Early in the rehabilitation process it will be used under supervision of a therapist, but with greatly reduced need for physical support from the therapists. This is intended to reduce the need for help from others and increase freedom of movement and personal autonomy of the patient”, said Ignacio Bermejo, Market Innovation Director at IBV.

One of the novelties of this device consists of a vest with attachment points on the patient’s waist in order to regulate the mobility of the trunk. Also, the device will be modular and low cost. The role of IBV in this initiative has been to define the design specifications and preclinical testing to validate the prototype. Preclinical tests are done in collaboration with the Department of Physical Medicine and Rehabilitation at the Hospital Universitari i Politècnic La Fe of Valencia.

The project is coordinated by the Norwegian company Made for Movement Group. Besides Biomechanics Institute, other members of the consortium are Innovatsiooni Eesti Instituut (Estonia), INNORA ROBOTICS (Greece), Newtrim and MCT (UK), ENIX (France), Motus (Italy) and MOBILE ROBOTICS SWEDEN (Sweden).

Stroke (cerebrovascular accident) is the most common cause of adult disability in Europe. Roughly 75% of victims survive, but about half of these lose the ability to live independently in their own home. As strokes often result in long term disability rather than death, the rehabilitation and hospitalisation represent a major economic burden for the EU of about €34 Bn annually. Currently, the annual incidence is approximately 2 per 1,000 inhabitants in the EU, and the number is predicted to double over the next 50 years due to the aging of the population.

Machine Perception Lab Shows Robotic One-Year-Old on Video

The world is getting a long-awaited first glimpse at a new humanoid robot in action mimicking the expressions of a one-year-old child. The robot will be used in studies on sensory-motor and social development – how babies “learn” to control their bodies and to interact with other people.

Diego-san’s hardware was developed by leading robot manufacturers: the head by Hanson Robotics, and the body by Japan’s Kokoro Co. The project is led by University of California, San Diego full research scientist Javier Movellan.

Movellan directs the Institute for Neural Computation’s Machine Perception Laboratory, based in the UCSD division of the California Institute for Telecommunications and Information Technology (Calit2). The Diego-san project is also a joint collaboration with the Early Play and Development Laboratory of professor Dan Messinger at the University of Miami, and with professor Emo Todorov’s Movement Control Laboratory at the University of Washington.

Movellan and his colleagues are developing the software that allows Diego-san to learn to control his body and to learn to interact with people.

"We’ve made good progress developing new algorithms for motor control, and they have been presented at robotics conferences, but generally on the motor-control side, we really appreciate the difficulties faced by the human brain when controlling the human body," said Movellan, reporting even more progress on the social-interaction side. "We developed machine-learning methods to analyze face-to-face interaction between mothers and infants, to extract the underlying social controller used by infants, and to port it to Diego-san. We then analyzed the resulting interaction between Diego-san and adults." Full details and results of that research are being submitted for publication in a top scientific journal.

While photos and videos of the robot have been presented at scientific conferences in robotics and in infant development, the general public is getting a first peak at Diego-san’s expressive face in action. On January 6, David Hanson (of Hanson Robotics) posted a new video on YouTube.

“This robotic baby boy was built with funding from the National Science Foundation and serves cognitive A.I. and human-robot interaction research,” wrote Hanson. “With high definition cameras in the eyes, Diego San sees people, gestures, expressions, and uses A.I. modeled on human babies, to learn from people, the way that a baby hypothetically would. The facial expressions are important to establish a relationship, and communicate intuitively to people.”

Diego-san is the next step in the development of “emotionally relevant” robotics, building on Hanson’s previous work with the Machine Perception Lab, such as the emotionally responsive Albert Einstein head.

Networking Ability a Family Trait in Monkeys

Two years of painstaking observation on the social interactions of a troop of free-ranging monkeys and an analysis of their family trees has found signs of natural selection affecting the behavior of the descendants. 

Rhesus macaques who had large, strong networks tended to be descendants of similarly social macaques, according to a Duke University team of researchers. And their ability to recognize relationships and play nice with others also won them more reproductive success. 

"If you are a more social monkey, then you’re going to have greater reproductive success, meaning your babies are more likely to survive their first year," said post-doctoral research fellow Lauren Brent, who led the study. "Natural selection appears to be favoring pro-social behavior."

The analysis, which appears in Nature Scientific Reports, combined sophisticated social network maps with 75 years of pedigree data and some genetic analysis.

Stem Cells May Hold Promise for Lou Gehrig’s Disease (ALS)

Apparent stem cell transplant success in mice may hold promise for people with amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. The results of the study were released today and will be presented at the American Academy of Neurology’s 65th Annual Meeting in San Diego, March 16 to 23, 2013. “There have been remarkable strides in stem cell transplantation when it comes to other diseases, such as cancer and heart failure,” said study author Stefania Corti, MD, PhD, with the University of Milan in Italy and a member of the American Academy of Neurology. “ALS is a fatal, progressive, degenerative disease that currently has no cure. Stem cell transplants may represent a promising avenue for effective cell-based treatment for ALS and other neurodegenerative diseases.”

For the study, mice with an animal model of ALS were injected with human neural stem cells taken from human induced pluripotent stem cells (iPSCs). iPSC are adult cells such as skin cells that have been genetically reprogrammed to an embryonic stem cell-like state. Neurons are a basic building block of the nervous system, which is affected by ALS. After injection, the stem cells migrated to the spinal cord of the mice, matured and multiplied.

The study found that stem cell transplantation significantly extended the lifespan of the mice by 20 days and improved their neuromuscular function by 15 percent. “Our study shows promise for testing stem cell transplantation in human clinical trials,” said Corti.

(Image: ALAMY)