Posts tagged brain damage
Articles and news from the latest research reports.
Study IDs new cause of brain bleeding immediately after stroke
By discovering a new mechanism that allows blood to enter the brain immediately after a stroke, researchers at UC Irvine and the Salk Institute have opened the door to new therapies that may limit or prevent stroke-induced brain damage.
A complex and devastating neurological condition, stroke is the fourth-leading cause of death and primary reason for disability in the U.S. The blood-brain barrier is severely damaged in a stroke and lets blood-borne material into the brain, causing the permanent deficits in movement and cognition seen in stroke patients.
Dritan Agalliu, assistant professor of developmental & cell biology at UC Irvine, and Axel Nimmerjahn of the Salk Institute for Biological Studies developed a novel transgenic mouse strain in which they use a fluorescent tag to see the tight, barrier-forming junctions between the cells that make up blood vessels in the central nervous system. This allows them to perceive dynamic changes in the barrier during and after strokes in living animals.
While observing that barrier function is rapidly impaired after a stroke (within six hours), they unexpectedly found that this early barrier failure is not due to the breakdown of tight junctions between blood vessel cells, as had previously been suspected. In fact, junction deterioration did not occur until two days after the event.
Instead, the scientists reported dramatic increases in carrier proteins called serum albumin flowing directly into brain tissue. These proteins travel through the cells composing blood vessels – endothelial cells – via a specialized transport system that normally operates only in non-brain vessels or immature vessels within the central nervous system. The researchers’ work indicates that this transport system underlies the initial failure of the barrier, permitting entry of blood material into the brain immediately after a stroke (within six hours).
“These findings suggest new therapeutic directions aimed at regulating flow through endothelial cells in the barrier after a stroke occurs,” Agalliu said, “and any such therapies have the potential to reduce or prevent stroke-induced damage in the brain.”
His team is currently using genetic techniques to block degradation of the tight junctions between endothelial cells in mice and examining the effect on stroke progression. Early post-stroke control of this specialized transport system identified by the Agalliu and Nimmerjahn labs may spur the discovery of imaging methods or biomarkers in humans to detect strokes as early as possible and thereby minimize damage.
New therapy helps to improve stereoscopic vision in stroke patients
Humans view the world through two eyes, but it is our brain that combines the images from each eye to form a single composite picture. If this function becomes damaged, impaired sight can be the result. Such loss of visual function can be observed in patients who have suffered a stroke or traumatic brain injury or when the oxygen supply to the brain has been reduced (cerebral hypoxia). Those affected by this condition experience blurred vision or can start to see double after only a short period of visual effort. Other symptoms can include increased fatigue or headaches. It is been suggested that these symptoms arise because the brain is unable to maintain its ability to fuse the separate images from each eye into a single composite image over a longer period. Experts refer to this phenomenon as binocular fusion dysfunction.
‘As a result, these patients have significantly reduced visual endurance,’ explains Katharina Schaadt, a graduate psychology student at Saarland University. ‘This often severely limits a patient’s ability to work or go about their daily life.’ Working at a computer screen or reading the newspaper can be very challenging. As binocular fusion is a fundamental requirement for achieving a three-dimensional impression of depth, those affected also frequently suffer from partial or complete stereo blindness. ‘Patients suffering from stereo blindness are no longer able to perceive spatial depth correctly,’ says Schaadt. ‘In extreme cases, the world appears as flat as a two-dimensional picture. Such patients may well have difficulties in reaching for an object, climbing stairs or walking on uneven ground.’
Although about 20% of stroke patients and up to 50% of patients with brain trauma injuries suffer from these types of functional impairments, there is still no effective therapy. Researchers at Saarland University working with Anna Katharina Schaadt and departmental head Professor Georg Kerkhoff have now developed a novel therapeutic approach and have examined its efficacy in two studies. ‘Test subjects underwent a six week training program in which both eyes were exercised equally,’ explains Schaadt. The aim was to train binocular fusion and thus improve three-dimensional vision. Participants in the study were presented with two images with a slight lateral offset between them. By using what are known as convergent eye movements, patients try to fuse the two images to a single image. This involves directing the eyes inward towards the nose while always keeping the images in the field of view. With time, the two images fuse to form a single image that exhibits stereoscopic depth, i.e. the patient has re-established binocular single vision.
The team of clinical neuropsychologists at Saarland University have used this training programme on eleven stroke patients, nine patients with brain trauma injury and four hypoxia patients. After completing the training programme, a significant improvement in binocular fusion and stereoscopic vision was observed in all participants. In many cases, a normal level of stereovision was attained. ‘The results remained stable in the two post-study examinations that we performed after three and six months respectively,’ says Schaadt. ‘Visual endurance also improved significantly.’ Patients who were able to work at a computer for only 15 to 20 minutes before they began treatment found that they could work at a computer screen for up to three hours after completing the therapeutic training programme.
The results are also of theoretical value to the Saarbrücken scientists, as they provide insight into brain function and indicate that certain regions of the brain that have been become damaged can be reactivated if the appropriate therapy is used.
Stem Cells Show Promise for Stroke Recovery
Early study found they can be safely transplanted into the brain; 2 patients showed significant improvement
In an early test, researchers report they’ve safely injected stem cells into the brains of 18 patients who had suffered strokes. And two of the patients showed significant improvement.
All the patients saw some improvement in weakness or paralysis within six months of their procedures. Although three people developed complications related to the surgery, they all recovered. There were no adverse reactions to the transplanted stem cells themselves, the study authors said.
What’s more, the researchers said, two patients experienced dramatic recoveries almost immediately after the treatments.
Those patients, who were both women, started to regain the ability to talk and walk the morning after their operations. In both cases, they were more than two years past their strokes, a point where doctors wouldn’t have expected further recovery.
Cell-saving drugs could reduce brain damage after stroke
Long-term brain damage caused by stroke could be reduced by saving cells called pericytes that control blood flow in capillaries, suggest researchers from Oxford University, UCL and the University of Copenhagen.
Until now, many scientists believed that blood flow within the brain was solely controlled by changes in the diameter of arterioles, blood vessels that branch out from arteries into smaller capillaries.
In this new study, the UK and Danish researchers reveal that the brain’s blood supply is in fact chiefly controlled by the narrowing or widening of capillaries as pericytes tighten or loosen around them.
Their study, published this week in the journal Nature, shows not only that pericytes are the main regulator of blood flow to the brain, but also that they tighten and die around capillaries after stroke. This significantly impairs blood flow in the long term, causing lasting damage to brain cells.
The scientists showed that certain chemicals can halve pericyte death from simulated stroke in the lab, and they hope to develop these into drugs to treat stroke victims.
'This discovery offers radically new treatment approaches for stroke,' says study co-author Professor Alastair Buchan, Dean of Medicine and Head of the Medical Sciences Division at Oxford University. 'Importantly, we should now be able to identify drugs that target these cells. If we are able to prevent pericytes from dying, it should help restore blood flow in the brain to normal and prevent the ongoing slow damage we see after a stroke which causes so much neurological disability in our patients.'
Professor David Attwell of UCL, who led the study, explains: ‘At present, clinicians can remove clots blocking blood flow to the brain if stroke patients reach hospital early enough. However, the capillary constriction produced by pericytes may, by restricting the blood supply for a long time, cause further damage to nerve cells even after the clot is removed. Our latest research suggests that devising drugs to prevent capillary constriction may offer new therapies for reducing the disability caused by stroke.’
The new research also gives insight into the mechanisms underlying the use of functional magnetic resonance imaging to detect blood flow changes in the brain.
'Functional imaging allows us to see the activity of nerve cells within the human brain but until now we didn't quite know what we were looking at,' says Professor Martin Lauritzen of the University of Copenhagen. 'We have shown that pericytes initiate the increase in blood flow seen when nerve cells become active. So we now know that functional imaging signals are caused by a pericyte-mediated increase of capillary diameter. Knowing exactly what functional imaging shows will help us to better understand and interpret what we see.'
(Source: ox.ac.uk)
Scientists catch brain damage in the act
Scientists have uncovered how inflammation and lack of oxygen conspire to cause brain damage in conditions such as stroke and Alzheimer’s disease.
The discovery, published today in Neuron, brings researchers a step closer to finding potential targets to treat neurodegenerative disorders.
Chronic inflammation and hypoxia, or oxygen deficiency, are hallmarks of several brain diseases, but little was known about how they contribute to symptoms such as memory loss.
The study used state-of-the-art techniques that reveal the movements of microglia, the brain’s resident immune cells. Brain researcher Brian MacVicar had previously captured how they moved to areas of injury to repair brain damage.
The new study shows that the combination of inflammation and hypoxia activates microglia in a way that persistently weakens the connection between neurons. The phenomenon, known as long-term depression, has been shown to contribute to cognitive impairment in Alzheimer’s disease.
“This is a never-before-seen mechanism among three key players in the brain that interact together in neurodegenerative disorders,” says MacVicar with the Djavad Mowafaghian Centre for Brain Health at UBC and Vancouver Coastal Health Research Institute.
“Now we can use this knowledge to start identifying new potential targets for therapy.”
Touching the brain
By examining the sense of touch in stroke patients, a University of Delaware cognitive psychologist has found evidence that the brains of these individuals may be highly plastic even years after being damaged.
The research is published in the March 6 edition of the journal Current Biology, in an article written by Jared Medina, assistant professor of psychology at UD, and Brenda Rapp of Johns Hopkins University’s Department of Cognitive Science. The findings, which are focused on patients who lost the sense of touch in their hands after a stroke, also have potential implications for other impairments caused by brain damage, Medina said.
“Our lab is interested in how the brain represents the body, not just in the sense of touch,” he said. “That involves a lot of different areas of the brain.”
For decades, scientists have been mapping the brain to determine which areas control certain functions, from movement to emotion to memory. In terms of representing the sense of touch, researchers know which specific parts of the brain are associated with representing specific parts of the body, Medina said.
Those scientists also know that, following the brain damage a stroke causes, patients often regain some of what they initially lost due to that damage.
“Even if every neuron has been killed in the part of the brain that represents touch on the hand, that doesn’t mean that you’re never going to feel anything on your hand again,” Medina said. “We’ve known that isn’t the case because the map can reorganize. The brain can change due to injury.”
But what the new research by Medina and Rapp found is that the brains of those stroke patients may change much more easily than the undamaged brains of healthy people — what they call “hyper-lability.”
The researchers worked with people who had had strokes in the past that affected their ability to localize touch. Each research participant, without being able to see his hand, was touched on the wrist and then on the fingertips. When asked to pinpoint the second touch, the stroke patients reported sensing the touch farther down their finger, toward the wrist, rather than in its actual location.
Medina says that likely occurs because the neural map in the brain is shifting based on the earlier wrist touch — a phenomenon termed “experience-dependent plasticity.”
“Now what’s interesting about this is that when you and I [who haven’t had a stroke] are touched on the wrist, then the fingertips, we don’t have these changes that the brain-damaged individuals do,” he said. “This provides the counterintuitive finding that the maps in brain-damaged individuals are actually much more plastic than in you and me.”
Hyper-plasticity has positive and negative implications, he said.
“On the positive side, this plasticity may potentially be harnessed in rehabilitation to improve function” after a stroke or various other types of brain injury, Medina said. But, he added, the brain may also be so plastic in those cases that changes aren’t stable, creating additional problems.
That’s what he expects additional research to address.
“Now that we’ve found that these maps are more plastic than we thought, can certain strategies help the map become more stable and more accurate again? That’s one of the next questions, and we can only answer it by continuing to learn more about how the mind works.”
(Source: udel.edu)
Brain Damage in Children—The Result of Too Many Chemicals?
A new report is sounding the alarm of a “silent epidemic” of childhood neurological disorders linked to neurotoxic compounds.
While genetics is known to play a role in neurological problems, only 30 to 40 percent of neurodevelopmental disorders can be definitively tied to family history. “There are a lot of chemicals out there that have been shown to have the capability to injure the developing brain,” says study coauthor Philip Landrigan, MD, professor and chair of the department of community and preventive medicine at Mount Sinai School of Medicine in New York City and one of the world’s foremost authorities on children’s environmental health. “And we’re very concerned that a number of chemicals in everyday products have never been properly tested to determine whether they’re toxic to the human brain.”
In the new report, Dr. Landrigan and his coauthor identified six chemicals that have been discovered, within the past seven years, to trigger brain damage in children. In 2006, he and other researchers ID’d lead, methylmercury, arsenic, polychlorinated biphenyls (PCBs), and toluene as known contributors to rising rates of neurodevelopmental disorders like autism, attention-deficit hyperactivity disorder, and learning disabilities.
Brain Implants Hold Promise Restoring Combat Memory Loss
The Pentagon is exploring the development of implantable probes that may one day help reverse some memory loss caused by brain injury.
The goal of the project, still in early stages, is to treat some of the more than 280,000 troops who have suffered brain injuries since 2000, including in combat in Iraq and Afghanistan.
The Defense Advanced Research Projects Agency is focused on wounded veterans, though some research may benefit others such as seniors with dementia or athletes with brain injuries, said Geoff Ling, a physician and deputy director of Darpa’s Defense Sciences office. It’s still far from certain that such work will result in an anti-memory-loss device. Still, word of the project is creating excitement after more than a decade of failed attempts to develop drugs to treat brain injury and memory loss.
“The way human memory works is one of the great unsolved mysteries,” said Andres Lozano, chairman of neurosurgery at the University of Toronto. “This has tremendous value from a basic science aspect. It may have huge implications for patients with disorders affecting memory, including those with dementia and Alzheimer’s disease.”
At least 1.7 million people in the U.S. are diagnosed with memory loss each year, costing the nation’s economy more than $76 billion annually, according to the most recent federal health data. The Department of Veterans Affairs estimates it will spend $4.2 billion to care for former troops with brain injuries between fiscal 2013 and 2022.
Neural prosthesis restores behavior after brain injury
Scientists from Case Western Reserve University and University of Kansas Medical Center have restored behavior—in this case, the ability to reach through a narrow opening and grasp food—using a neural prosthesis in a rat model of brain injury.
Ultimately, the team hopes to develop a device that rapidly and substantially improves function after brain injury in humans. There is no such commercial treatment for the 1.5 million Americans, including soldiers in Afghanistan and Iraq, who suffer traumatic brain injuries (TBI), or the nearly 800,000 stroke victims who suffer weakness or paralysis in the United States, annually.
The prosthesis, called a brain-machine-brain interface, is a closed-loop microelectronic system. It records signals from one part of the brain, processes them in real time, and then bridges the injury by stimulating a second part of the brain that had lost connectivity.
Their work is published online this week in the science journal Proceedings of the National Academy of Sciences.
“If you use the device to couple activity from one part of the brain to another, is it possible to induce recovery from TBI? That’s the core of this investigation,” said Pedram Mohseni, professor of electrical engineering and computer science at Case Western Reserve, who built the brain prosthesis.
“We found that, yes, it is possible to use a closed-loop neural prosthesis to facilitate repair of a brain injury,” he said.
The researchers tested the prosthesis in a rat model of brain injury in the laboratory of Randolph J. Nudo, professor of molecular and integrative physiology at the University of Kansas. Nudo mapped the rat’s brain and developed the model in which anterior and posterior parts of the brain that control the rat’s forelimbs are disconnected.
Atop each animal’s head, the brain-machine-brain interface is a microchip on a circuit board smaller than a quarter connected to microelectrodes implanted in the two brain regions.
The device amplifies signals, which are called neural action potentials and produced by the neurons in the anterior of the brain. An algorithm separates these signals, recorded as brain spike activity, from noise and other artifacts. With each spike detected, the microchip sends a pulse of electric current to stimulate neurons in the posterior part of the brain, artificially connecting the two brain regions.
Two weeks after the prosthesis had been implanted and run continuously, the rat models using the full closed-loop system had recovered nearly all function lost due to injury, successfully retrieving a food pellet close to 70 percent of the time, or as well as normal, uninjured rats. Rat models that received random stimuli from the device retrieved less than half the pellets and those that received no stimuli retrieved about a quarter of them.
“A question still to be answered is must the implant be left in place for life?” Mohseni said. “Or can it be removed after two months or six months, if and when new connections have been formed in the brain?”
Brain studies have shown that, during periods of growth, neurons that regularly communicate with each other develop and solidify connections.
Mohseni and Nudo said they need more systematic studies to determine what happens in the brain that leads to restoration of function. They also want to determine if there is an optimal time window after injury in which they must implant the device in order to restore function.
(Source: blog.case.edu)
Baylor Research Institute Studies Traumatic Brain Injury Rehab Outcomes
For patients recovering from a traumatic brain injury (TBI), the rehabilitation process – compensating for changes in functioning, adaptation and even community reintegration – can be challenging. Unfortunately, not all rehab programs are created equal, and with the differences comes a difference in outcomes, according to a first-of-its-kind study published in The Journal of Head Trauma Rehabilitation.
Collectively authored by Baylor researchers, the outcomes study (titled “Comparative Effectiveness of Traumatic Brain Injury Rehabilitation: Differential Outcomes Across TBI Model Systems Centers”), set out to identify if outcomes at the post-discharge and one-year points varied across 21 Traumatic Brain Injury Model System (TBIMS) centers. The Baylor Institute of Rehabilitation (BIR) was one of the centers studied.
At the study’s onset, researchers had an idea of what they might find, but their findings revealed the opposite.
“We expected that, after accounting for differences in patient characteristics and severity of injury, patient outcomes would be similar across centers,” said Marie Dahdah, PhD, investigator at the Baylor Institute for Rehabilitation. “They were not. There were significant variations, with a 25 percent to 45 percent difference between the best performing site and the site with the lowest outcomes at discharge.”
While differences in outcomes have long been reported in designated trauma centers (and for other specialties, including general and cardiac surgery, transplant and oncology), the study was the first piece of research to demonstrate that those differences exist in the rehabilitation context.
The team acknowledged that those variances could be attributed to institutional structures, resources and clinical practices, but that more research is needed to determine which of these factors is associated with optimum outcomes.
“In order to identify factors that contribute to variation in patient outcomes across centers, we are undertaking research that identifies different patient, injury and process-level factors associated with functional outcomes of patients,” Dr. Dahdah said. “Those factors can then be targeted to improve patient outcomes.”
In other phases of this study, these Baylor investigators (along with teams from three other TBIMS sites) are reviewing the quantity and frequency of various types of rehabilitation therapies used in inpatient TBI settings. The team will also study evidenced-based best practices for speech, occupational, physical and recreational therapy interventions, as well as neurocognitive and psychosocial interventions.
The results from those subsequent studies could help identify gaps between current practices and evidence-based best practices, with the aim of helping inform rehabilitation programs across the country and ensuring that all centers have the same opportunities for quality outcomes.
“I think I speak for my entire research team when I say that our involvement in this type of research comes out of our collective desire to improve quality of rehabilitation care, thereby enhancing outcomes following TBI,” Dr. Dahdah said. “My hope is that by synthesizing and disseminating what is known about effective evidence-based rehabilitation interventions, BIR as part of the North Texas TBIMS will be able to encourage changes necessary to help institutions, clinicians and therapists to provide the best quality TBI rehabilitation care to their patients.”
Of course, with the Baylor Institute of Rehabilitation being among the 21-center pool, one very obvious question remains. How did BIR’s outcomes compare with the other 20 centers?
“I cannot count for you the number of times I have been asked that question,” Dr. Dahdah said. “To ensure the integrity of our study, even our research team is blind to the identity of the centers.”
But despite how well even the strongest inpatient rehab centers perform in a comparative context, there is always room for improvement, especially with best-practice regimens.
“Our research has already started discussions within the TBI Model Systems research community,” Dr. Dahdah said. “We believe more research needs to be done to identify the key determinants of patient outcomes so that benchmarks for quality rehabilitation care can be derived for patients and their families.”
(Source: media.baylorhealth.com)