Posts tagged brain injury
Articles and news from the latest research reports.
Study finds cognitive performance can be improved in teens months,years after traumatic brain injury
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)
Risk of brain injury is genetic
University researchers have identified a link between injury to the developing brain and common variation in genes associated with schizophrenia and the metabolism of fat.
The study builds on previous research, which has shown that being born prematurely - before 37 weeks - is a leading cause of learning and behavioural difficulties in childhood.
Around half of infants weighing less than 1500g at birth go on to experience difficulties in learning and attention at school age.
Unique collaboration
Scientists at Edinburgh, Imperial College London and King’s College London studied genetic samples and MRI scans of more than 80 premature infants at the time of discharge from hospital.
The tests and scans revealed that variation in the genetic code of genes known as ARVCF and FADS2 influenced the risk of brain injury on MRI in the babies.
Global challenge
Premature births account for 10 per cent of all births worldwide, according to experts.
Earlier research has shown that being born preterm is closely related to abnormal brain development and poor neurodevelopmental outcome.
However, scientists say that they do not fully understand the processes that lead to these problems in some infants.
Researchers add that future studies could look at how changes in these genes may bring about this risk of - or resilience - to brain injury.
Environmental factors such as degree of prematurity at birth and infection play a part, but, as our study has found, they are not the whole story and genetic factors have a role in conferring risk or resilience. We hope that our findings will lead to new understanding about the mechanisms that lead to brain injury and ultimately new neuroprotective treatment strategies for preterm babies.-Dr James Boardman (Scientific director of the Jennifer Brown Research Laboratory at the MRC Centre for Reproductive Health at the University of Edinburgh)
(Image: Thinkstock)
Older migraine sufferers may have more silent brain injury
Older migraine sufferers may be more likely to have silent brain injury, according to research published in the American Heart Association’s journal Stroke.
In a new study, people with a history of migraine headaches had double the odds of ischemic silent brain infarction compared to people who said they didn’t have migraines. Silent brain infarction is a brain injury likely caused by a blood clot interrupting blood flow to brain tissue. Sometimes called “silent strokes,” these injuries are symptomless and are a risk factor for future strokes.
Previous studies indicated migraine could be an important stroke risk factor for younger people.
“I do not believe migraine sufferers should worry, as the risk of ischemic stroke in people with migraine is considered small,” said Teshamae Monteith, M.D., lead author of the study and assistant professor of clinical neurology and chief of the Headache Division at the University of Miami Miller School of Medicine. “However, those with migraine and vascular risk factors may want to pay even greater attention to lifestyle changes that can reduce stroke risk, such as exercising and eating a low-fat diet with plenty of fruits and vegetables.”
High blood pressure, another important stroke risk factor, was more common in those with migraine. But the association between migraine and silent brain infarction was also found in participants with normal blood pressure.
Because Hispanics and African-Americans are at increased stroke risk, researchers from the Northern Manhattan Study (NOMAS) – a collaborative investigation between the University of Miami and Columbia University – studied a multi-ethnic group of older adults (41 percent men, average age 71) in New York City. About 65 percent of participants were Hispanic. Comparing magnetic resonance imaging results between 104 people with a history of migraine and 442 without, they found:
- A doubling of silent brain infarctions in those with migraine even after adjusting for other stroke risk factors;
- No increase in the volume of white-matter hyperintensities (small blood vessel abnormalities) that have been associated with migraine in other studies;
- Migraines with aura — changes in vision or other senses preceding the headache — wasn’t common in participants and wasn’t necessary for the association with silent cerebral infarctions.
“While the lesions appeared to be ischemic, based on their radiographic description, further research is needed to confirm our findings,” Monteith said.
The research raises the question of whether preventive treatment to reduce the severity and number of migraines could reduce the risk of stroke or silent cerebral infarction.
“We still don’t know if treatment for migraines will have an impact on stroke risk reduction, but it may be a good idea to seek treatment from a migraine specialist if your headaches are out of control,” Monteith said.
Tracking the Source of “Selective Attention” Problems in Brain-Injured Vets
An estimated 15-20 percent of U.S. troops returning from Iraq and Afghanistan suffer from some form of traumatic brain injury (TBI) sustained during their deployment, with most injuries caused by blast waves from exploded military ordnance. The obvious cognitive symptoms of minor TBI — including learning and memory problems — can dissipate within just a few days. But blast-exposed veterans may continue to have problems performing simple auditory tasks that require them to focus attention on one sound source and ignore others, an ability known as “selective auditory attention.”
According to a new study by a team of Boston University (BU) neuroscientists, such apparent “hearing” problems actually may be caused by diffuse injury to the brain’s prefrontal lobe — work that will be described at the 167th meeting of the Acoustical Society of America, to be held May 5-9, 2014 in Providence, Rhode Island.
"This kind of injury can make it impossible to converse in everyday social settings, and thus is a truly devastating problem that can contribute to social isolation and depression," explains computational neuroscientist Scott Bressler, a graduate student in BU’s Auditory Neuroscience Laboratory, led by biomedical engineering professor Barbara Shinn-Cunningham.
For the study, Bressler, Shinn-Cunningham and their colleagues — in collaboration with traumatic brain injury and post-traumatic stress disorder expert Yelena Bogdanova of VA Healthcare Boston — presented a selective auditory attention task to 10 vets with mild TBI and to 17 control subjects without brain injuries. Notably, on average, veterans had hearing within a normal range.
In the task, three different melody streams, each comprised of two notes, were simultaneously presented to the subjects from three different perceived directions (this variation in directionality was achieved by differing the timing of the signals that reached the left and right ears). The subjects were then asked to identify the “shape” of the melodies (i.e., “going up,” “going down,” or “zig-zagging”) while their brain activity was measured by electrodes on the scalp.
"Whenever a new sound begins, the auditory cortex responds, encoding the sound onset," Bressler explains. "Attentional focus, however, changes the strength of this response: when a listener is attending to a particular sound source, the neural activity in response to that sound is greater." This change of the neural response occurs because the brain’s "executive control" regions, located in the brain’s prefrontal cortex, send signals to the auditory sensory regions of the brain, modulating their response.
The researchers found that blast-exposed veterans with TBI performed worse on the task — that is, they had difficulty controlling auditory attention — “and in all of the TBI veterans who performed well enough for us to measure their neural activity, 6 out of our 10 initial subjects, the brain response showed weak or no attention-related modulation of auditory responses,” Bressler says.
"Our hope is that some of our findings can be used to develop methods to assess and quantify TBI, identifying specific factors that contribute to difficulties communicating in everyday settings," he says. "By identifying these factors on an individual basis, we may be able to define rehabilitation approaches and coping strategies tailored to the individual."
Some TBI patients also go on to develop chronic traumatic encephalopathy (CTE) — a debilitating progressive degenerative disease with symptoms that include dementia, memory loss and depression — which can now only be definitively diagnosed after death. “With any luck,” Bressler adds, “neurobehavioral research like ours may help identify patients at risk of developing CTE long before their symptoms manifest.”
(Source: newswise.com)
Engineering resilience in the brain
Penn researchers model neural structures on the smallest scales to better understand traumatic brain injury
Compared to the monumental machines of science, things like the International Space Station or the Large Hadron Collider, the human brain doesn’t look like much. However, this three-pound amalgam of squishy cells is one of the most complicated and complex structures in the known universe.
With hundreds of billions of neurons, each with its own inner world of organelles and molecular components, understanding the fundamental wiring of the brain is a major undertaking, one that has received a commitment of at least $100 million worth of federal funding from the National Science Foundation (NSF), the National Institutes of Health and the Defense Advanced Research Projects Agency.
And with all of the brain’s interconnected structures, protecting or repairing this complicated machine means thinking like an engineer.
"The idea is really quite simple," says Vivek Shenoy, an NSF-supported professor of materials science and engineering at the University of Pennsylvania’s School of Engineering and Applied Science. "All of the mechanical properties of cells come from their cytoskeleton and the molecules within it. They’re all reinforcing frames, like the frame in a building. Engineers design buildings and other structural objects to make sure they don’t fail, so it’s the same principle: structural engineering on a very, very small level."
Shenoy applies this approach to a problem very much in the public eye—traumatic brain injury. Even the mildest forms of TBI, better known as concussions, can do irreversible damage to the brain. More serious forms can be fatal.
With a background in mechanical engineering and materials science, one might think that Shenoy’s contribution to this problem involves designing new helmets or other safety devices. Instead, he and his colleagues are uncovering the fundamental math and physics behind one of the core mechanisms of the injury: swelling in axons caused by damage to internal structures known as microtubules. These neural “train tracks” transport molecular cargo from one end of a neuron to another; when the tracks break, the cargo piles up and produces bulges in the axons that are the hallmark of fatal TBIs.
Armed with a better understanding of the mechanical properties of these critical structures, Shenoy and his colleagues are laying the foundations for drugs that could one day bolster neurons’ reinforcing frames, making them more resilient when faced with a TBI-inducing impact.
Train tracks and crossties
The first step toward this understanding was resolving a paradox: Why were the microtubules, the stiffest elements of the axons, the parts that were breaking when loaded with the stress of a blow to the head?
A recent finding from Shenoy’s team shows that the answer rests with a critical brain protein known as tau, which is implicated in several neurodegenerative diseases, including Alzheimer’s. If microtubules are like train tracks, tau proteins are the crossties that hold them together. The protein’s elastic properties help explain why rapid movement of the brain, whether on a football field or a car crash, leads to TBI.
Shenoy’s colleague Douglas Smith, professor of neurosurgery in Penn’s Perelman School of Medicine and director of the Penn Center for Brain Injury and Repair, had previously studied the mechanical properties of axons, subjecting them to strains of different forces and speeds.
"What we saw is that with slow loading rates, axons can stretch up to at least 100 percent with no signs of damage," Smith said. "But at faster rates, axons start displaying the same swellings you see in the TBI patients. This process occurs even with relatively short stretches at fast rates."
To explain this rate-dependent response, Shenoy and Smith had to delve deeper inside the structure of microtubules. Based on Smith’s work, other biophysical modelers had previously accounted for the geometry and elastic properties of the axon during a stretching injury, but they did not have good data for representing tau’s role.
"You need to know the elastic properties of tau," Shenoy said, "because when you load the microtubules with stress, you load the tau as well. How these two parts distribute the stress between them is going to have major impact on the system as a whole."
Elastic properties
Shenoy and his colleagues had a sense of tau’s elastic properties but did not have hard numbers until a 2011 experiment from a Swiss and German research team physically stretched out lengths of tau by plucking it with the tip of an atomic force microscope.
"This experiment demonstrated that tau is viscoelastic," Shenoy said. "Like Silly Putty, when you add stress to it slowly, it stretches a lot. But if you add stress to it rapidly, like in an impact, it breaks."
This behavior is because the strands of tau protein are coiled up and bonded to themselves in different places. Pulled slowly, those bonds can come undone, lengthening the strand without breaking it.
"The damage in traumatic brain injury occurs when the microtubules stretch but the tau doesn’t, as they can’t stretch as far," Shenoy said. "If you’re in a situation where the tau doesn’t stretch, such as what happens in fast strain rates, then all the strain will transfer to the microtubules and cause them to break."
With a comprehensive model of the tau-microtubule system, the researchers were able to boil down the outcome of rapid stress loading to equations with only a handful of variables. This mathematical understanding allowed the researchers to produce a phase diagram that shows the dividing line between strain rates that leave permanent damage versus ones that are safe and reversible.
Next steps
Having this mathematical understanding of the interplay between tau and microtubules is only the beginning.
"Predicting what kind of impacts will cause these strain rates is still a complicated problem," Shenoy said. "I might be able to measure the force of the impact when it hits someone’s head, but that force then has to make its way down to the axons, which depends on a lot of different things.
"You need a multiscale model, and our work will be an input to those models on the smallest scale."
In the longer term, however, knowing the parameters that lead to irreversible damage could lead to better understanding of brain injuries and diseases and to new preventive measures. It may even be possible to design drugs that alter microtubule stability and elasticity of axons in traumatic brain injury; Smith’s group has demonstrated that treatment with the microtubule-stabilizing drug taxol reduced the extent of axon swellings and degeneration after injuries in which they are stretched.
Ultimately, insights on the molecular level will be inputs to a more comprehensive view of the brain and its many hierarchies of organizations.
"When you’re talking about something’s mechanical properties, stiffness is what comes to mind," Shenoy said. "Biochemistry is what determines that stiffness in the brain’s structures, but that’s only at the molecular level. Once you build it up and formulate things at the appropriate scale, protecting the brain becomes more of a structural engineering problem."
Model Sheds New Light on Sports-related Brain Injuries
A new study has provided insight into the behavioral damage caused by repeated blows to the head. The research provides a foundation for scientists to better understand and potentially develop new ways to detect and prevent the repetitive sports injuries that can lead to the condition known as chronic traumatic encephalopathy (CTE).
The research – which appears online this week in the Journal of Neurotrauma – shows that mice with mild, repetitive traumatic brain injury (TBI) develop many of the same behavioral problems, such as difficultly sleeping, memory problems, depression, judgment and risk-taking issues, that have been associated with the condition in humans.
One of the barriers to potential treatments for TBI and CTE is that no model of the disease exists. Animal equivalents of human diseases are a critical early-stage tool in the scientific process of understanding a condition, developing new ways to diagnose it, and evaluating experimental therapies.
“This new model captures both the clinical aspects of repetitive mild TBI and CTE,” said Anthony L. Petraglia, M.D., a neurosurgeon with the University of Rochester School of Medicine and Dentistry and lead author of the study. “While public awareness of the long-term health risk of blows to the head is growing rapidly, our ability to scientifically study the fundamental neurological impact of mild brain injuries has lagged.”
There has been a great deal of discussion in recent years regarding concussions as a result of blows to the head in sports. An estimated 3.8 million sports-related concussions occur every year. Mild traumatic brain injury is also becoming more common in military personnel deployed in combat zones. Over time, the frequency and degree of these injuries can lead short and long-term neurological impairment and, in extreme examples, to CTE, a form of degenerative brain disease.
The experiments described in the study were designed in a manner that simulates the type of mild TBI that may occur in sports or other blows to the head. The researchers evaluated the mice’s performance in a series of tasks designed to measure behavior. These included tests to measure spatial and learning memory, anxiety and risk-taking behavior, the presence of depression-like behavior, sleep disturbances, and the electrical activity of their brain. The mice with repetitive mild TBI did poorly in every test and this poor performance persisted over time.
“These results resemble the spectrum of neuro-behavioral problems that have been reported and observed in individuals who have sustained multiple mild TBI and those who were subsequently diagnosed with CTE, including behaviors such as poor judgment, risk taking, and depression,” said Petraglia.
Petraglia and his colleagues also used the model to examine the damage that was occurring in the brains of the mice over time. The results, which will be published in a forthcoming paper, provide insight on the interaction between the brains repair mechanisms – in the forms of astrocytes and microglia – and the protein tau, which can have a toxic effect when triggered by mild traumatic brain injury.
“Undoubtedly further work is needed,” said Petraglia. “However, this study serves as a good starting point and it is hoped that with continued investigation this novel model will allow for a controlled, mechanistic analysis of repetitive mild TBI and CTE in the future, because it is the first to encapsulate the spectrum of this human phenomenon.”
(Source: urmc.rochester.edu)
Zinc Supplementation Shows Promise in Reducing Cell Stress After Blasts
Each year, approximately 2 million traumatic brain injuries (TBIs) occur in the USA, according to the Centers for Disease Control and Prevention. That number includes troops wounded in Iraq and Afghanistan, for whom TBI is considered an invisible wound of war, one that has few successful treatments. “We have nothing beyond ibuprofen for most TBIs,” said Dr. Angus Scrimgeour, who has been investigating the effects of low zinc diets on cell stress following a blast injury. “The adult brain does not self-repair from this kind of trauma.”
Scrimgeour works for the US Army Research Institute of Environmental Medicine and recently looked at the effects of 5-weeks of low and adequate zinc diets on a specific protein in muscle cells called MMP. The study recreated blast injuries in 32 rats similar to what soldiers experience from IEDs, including loss of consciousness. An equal number of rats served as a control group. Results suggest that zinc supplementation reduces blast-induced cell stress. He presented the results of his research at the American Society for Nutrition’s Scientific Sessions & Annual Meeting at EB on Sunday, April 27.
“We know that soldiers’ brain tissue cannot repair on low zinc diets,” said Scrimgeour. “And they are losing zinc through diarrhea and sweating.” The question moving forward is whether prevention through diet supplementation or post-blast treatment works best to repair behavioral deficits associated with mild TBI.
Scrimgeour added that further research is planned to investigate nutrient combinations for treating mild TBI, including omega-3, vitamin D, glutamine and/or zinc. Although the Army is conducting this research, the results can be applied outside of the military, according to Scrimgeour. “As the blast impact experienced by Soldiers are similar to those experienced during head injuries received in a car accident or during an NFL concussion, these findings could translate from the Soldier to the civilian population.” Scrimgeour cautioned, however, that what works in animals doesn’t always work in soldiers, which is why more research is needed.
(Source: newswise.com)
Half of homeless men had traumatic brain injury
Study finds almost half of homeless men had traumatic brain injury in their lifetime, vast majority before they lost their homes
Almost half of all homeless men who took part in a study by St. Michael’s Hospital had suffered at least one traumatic brain injury in their life and 87 per cent of those injuries occurred before the men lost their homes.
While assaults were a major cause of those traumatic brain injuries, or TBIs, (60 per cent) many were caused by potentially non-violent mechanisms such as sports and recreation (44 per cent) and motor vehicle collisions and falls (42 per cent).
The study, led by Dr. Jane Topolovec-Vranic, a clinical researcher in the hospital’s Neuroscience Research Program, was published in the journal CMAJ Open.
Dr. Topolovec-Vranic said it’s important for health care providers and others who work with homeless people to be aware of any history of TBI because of the links between such injuries and mental health issues, substance abuse, seizures and general poorer physical health.
The fact that so many homeless men suffered a TBI before losing their home suggests such injuries could be a risk factor for becoming homeless, she said. That makes it even more important to monitor young people who suffer TBIs such as concussions for health and behavioural changes, she said.
Dr. Topolovec-Vranic looked at data on 111 homeless men aged 27 to 81 years old who were recruited from a downtown Toronto men’s shelter. She found that 45 per cent of these men had experienced a traumatic brain injury, and of these, 70 per cent were injured during childhood or teenage years and 87 per cent experienced an injury before becoming homeless.
In men under age 40, falls from drug/alcohol blackouts were the most common cause of traumatic brain injury while assault was the most common in men over 40 years old.
Recognition that a TBI sustained in childhood or early teenage years could predispose someone to homelessness may challenge some assumptions that homelessness is a conscious choice made by these individuals, or just the result of their addictions or mental illness, said Dr. Topolovec-Vranic.
This study received funding from the Canadian Institutes of Health Research and the Ontario Neurotrauma Foundation.
Separately, a recent study by Dr. Stephen Hwang of the hospital’s Centre for Research on Inner City Health, found the number of people who are homeless or vulnerably housed and who have also suffered a TBI may be as high as 61 per cent—seven times higher than the general population.
Dr. Hwang’s study, published in the Journal of Head Trauma Rehabilitation, is one of the largest studies to date investigating TBI in homeless populations. The findings come from the Health and Housing in Transition Study, which tracks the health and housing status of homeless and vulnerably housed people in Toronto, Vancouver and Ottawa.
(Source: stmichaelshospital.com)
Higher Education Associated With Better Recovery From Traumatic Brain Injury
Better-educated people appear to be significantly more likely to recover from a moderate to severe traumatic brain injury (TBI), suggesting that a brain’s “cognitive reserve” may play a role in helping people get back to their previous lives, new Johns Hopkins research shows.
The researchers, reporting in the journal Neurology, found that those with the equivalent of at least a college education are seven times more likely than those who didn’t finish high school to be disability-free one year after a TBI serious enough to warrant inpatient time in a hospital and rehabilitation facility.
The findings, while new among TBI investigators, mirror those in Alzheimer’s disease research, in which higher educational attainment — believed to be an indicator of a more active, or more effective, use of the brain’s “muscles” and therefore its cognitive reserve — has been linked to slower progression of dementia.
“After this type of brain injury, some patients experience lifelong disability, while others with very similar damage achieve a full recovery,” says study leader Eric B. Schneider, Ph.D., an epidemiologist at the Johns Hopkins University School of Medicine’s Center for Surgical Trials and Outcomes Research. “Our work suggests that cognitive reserve ¬— the brain’s ability to be resilient in the face of insult or injury — could account for the difference.”
Schneider conducted the research in conjunction with Robert D. Stevens. M.D., a neuro-intensive care physician with Johns Hopkins’ Department of Anesthesiology and Critical Care Medicine.
For the study, the researchers studied 769 patients enrolled in the TBI Model Systems database, an ongoing multi-center cohort of patients funded by the National Institute on Disability and Rehabilitation Research. The patients had been hospitalized with a moderate to severe TBI and subsequently admitted to a rehabilitation facility.
Of the 769 patients, 219 — or 27.8 percent — were free of any detectable disability one year after their injury. Twenty-three patients who didn’t complete high school — 9.7 percent of those at that education level — recovered, while 136 patients with between 12 and 15 years of schooling — 30.8 percent of those at that educational level — did. Nearly 40 percent of patients — 76 of the 194 — who had 16 or more years of education fully recovered.
Schneider says researchers don’t currently understand the biological mechanisms that might account for the link between years of schooling and improved recovery.
“People with increased cognitive reserve capabilities may actually heal in a different way that allows them to return to their pre–injury function and/or they may be able to better adapt and form new pathways in their brains to compensate for the injury,” Schneider says. “Further studies are needed to not only find out, but also to use that knowledge to help people with less cognitive reserve.”
Meanwhile, he says, “What we learned may point to the potential value of continuing to educate yourself and engage in cognitively intensive activities. Just as we try to keep our bodies strong in order to help us recover when we are ill, we need to keep the brain in the best shape it can be.”
Adds Stevens: “Understanding the underpinnings of cognitive reserve in terms of brain biology could generate ideas on how to enhance recovery from brain injury.”
(Source: hopkinsmedicine.org)
Commonly available blood-pressure drug prevents epilepsy after brain injury
Between 10 and 20 percent of all cases of epilepsy result from severe head injury, but a new drug promises to prevent post-traumatic seizures and may forestall further brain damage caused by seizures in those who already have epilepsy.
A team of researchers from UC Berkeley, Ben-Gurion University in Israel and Charité-University Medicine in Germany reports in the current issue of the journal Annals of Neurology that a commonly used hypertension drug prevents a majority of cases of post-traumatic epilepsy in a rodent model of the disease. If independent experiments now underway in rats confirm this finding, human clinical trials could start within a few years.
“This is the first-ever approach in which epilepsy development is stopped, as opposed to common drugs that try to prevent seizures once epilepsy develops,” said coauthor Daniela Kaufer, UC Berkeley associate professor of integrative biology and a member of the Helen Wills Neuroscience Institute. “Those drugs have a very limited success and many side effects, so we are excited about the new approach.”
The team, led by Kaufer; neurosurgeon Alon Friedman, associate professor of physiology and neurobiology at the Ben-Gurion University of the Negev; and Uwe Heinemann of the Charite, provides the first explanation for how brain injury caused by a blow to the head, stroke or infection leads to epilepsy. Based on 10 years of collaborative research, their findings point a finger at the blood-brain barrier – the tight wall of cells lining the veins and arteries in the brain that is breached after trauma.
“This study for the first time offers a new mechanism and an existing, FDA-approved drug to potentially prevent epilepsy in patients after brain injuries or after they develop an abnormal blood-brain barrier,” Friedman said.
The drug, losartan (Cozaar®), prevented seizures in 60 percent of the rats tested, when normally 100 percent of the rats develop seizures after injury. In the 40 percent of rats that did develop seizures, they averaged about one quarter the number of seizures typical for untreated rats. Another experiment showed that administration of losartan for three weeks at the time of injury was enough to prevent most cases of epilepsy in normal lab rats in the following months.
“This is a very exciting result, telling us that the drug worked to prevent the development of epilepsy and not by suppressing the symptoms,” Kaufer said.
Breakdown of the blood-brain barrier
Kaufer and Friedman have been collaboratively investigating the effects of trauma on the brain since Kaufer was a graduate student in Israel 20 years ago. Throughout a postdoctoral position at Stanford University and after joining the UC Berkeley faculty in 2005, she maintained her interest in the blood-brain barrier, which normally protects the brain from potentially damaging chemicals or bacteria in the blood and prevents brain chemicals from leaking into the blood stream.
She and Friedman showed earlier that breaking down the barrier causes inflammation and leads to the development of epilepsy. They pinned the effect to a single protein called albumin, the most common protein in blood serum.
In 2009, they showed that albumin affects astrocytes, the brain’s support cells, by binding to the TGF-β (transforming growth factor-beta) receptor. This initiates a cascade of steps that lead to localized inflammation, which appears to permanently damage the brain’s wiring, leading to the electrical misfiring characteristic of epilepsy. The current paper conclusively demonstrates that blocking the TGF-beta receptor with losartan stops that cascade and prevents the disorder.
Drug’s side effect proves crucial
Coauthor Guy Bar-Klein, a doctoral student at Ben-Gurion University, searched a long list of drugs before discovering losartan, which is approved to treat high blood pressure because it blocks the angiotensin receptor 1, but which incidentally also blocks TGF-β. It worked in the rats when delivered in their drinking water, which means that it somehow gets into the brain through the blood-brain barrier. The experiments suggest that the drug is unable to cross an intact blood-brain barrier, but reaches the brain through a breached barrier when it is most needed, Kaufer said.
Friedman developed a protocol to use MRI to check whether the blood brain barrier has been breached, allowing doctors to give losartan as a preventive treatment, if necessary, after trauma. Kaufer said that the barrier may remain open for only a few weeks after injury, so the drug would not have to be given very long to prevent damage.
“Right now, if someone comes to the emergency room with traumatic brain injury, they have a 10 to 50 percent chance of developing epilepsy, and epilepsy from brain injuries tends to be unresponsive to drugs in many patients.” she said. “I’m very hopeful that our research can spare these patients the added trauma of epilepsy.”