1. Researchers identify how inflammation spreads through the brain after injury

    March 26, 2017 by Ashley

    From the University of Maryland School of Medicine press release:

    Researchers have identified a new mechanism by which inflammation can spread throughout the brain after injury. This mechanism may explain the widespread and long-lasting inflammation that occurs after traumatic brain injury, and may play a role in other neurodegenerative diseases.

    The findings were published today in a study in the Journal of Neuroinflammation.

    This new understanding has the potential to transform how brain inflammation is understood, and, ultimately, how it is treated. The researchers showed that microparticles derived from brain inflammatory cells are markedly increased in both the brain and the blood following experimental traumatic brain injury (TBI). These microparticles carry pro-inflammatory factors that can activate normal immune cells, making them potentially toxic to brain neurons. Injecting such microparticles into the brains of uninjured animals creates progressive inflammation at both the injection site and eventually in more distant sites.

    Research has found that neuroinflammation often goes on for years after TBI, causing chronic brain damage. The researchers say that the microparticles may play a key role in this process.

    Chronic inflammation has been increasingly implicated in the progressive cell loss and neurological changes that occur after TBI. These inflammatory microparticles may be a key mechanism for chronic, progressive brain inflammation and may represent a new target for treating brain injury.

    The researchers on the paper include four University of Maryland School of Medicine researchers: Alan Faden, Stephen R. Thom, Bogdan A. Stoica, and David Loane.

    “These results potentially provide a new conceptual framework for understanding brain inflammation and its relationship to brain cell loss and neurological deficits after head injury, and may be relevant for other neurodegenerative disorders such as Alzheimer disease in which neuroinflammation may also play a role,” said Dr. Faden. “The idea that brain inflammation can trigger more inflammation at a distance through the release of microparticles may offer novel treatment targets for a number of important brain diseases.”

    The researchers studied mice, and found that in animals who had a traumatic brain injury, levels of microparticles in the blood were much higher. Because each kind of cell in the body has a distinct fingerprint, the researchers could track exactly where the microparticles came from. The microparticles they looked at in this study are released from cells known as microglia, immune cells that are common in the brain. After an injury, these cells often go into overdrive in an attempt to fix the injury. But this outsized response can change protective inflammatory responses to chronic destructive ones.

    The findings have important potential clinical implications. The researchers say that microparticles in the blood have the potential to be used as a biomarker — a way to determine how serious a brain injury may be. This could help guide treatment of the injuries, whose severity is often difficult to gauge.

    They also found that exposing the inflammatory microparticles to a compound called PEG-TB could neutralize them. This opens up the possibility of using that compound or others to treat TBI, and perhaps even other neurodegenerative diseases.


  2. Head injuries can alter hundreds of genes and lead to serious brain diseases

    March 23, 2017 by Ashley

    From the UCLA press release:

    Head injuries can harm hundreds of genes in the brain in a way that increases people’s risk for a wide range of neurological and psychiatric disorders, UCLA life scientists report.

    The researchers identified for the first time master genes that they believe control hundreds of other genes which are linked to Alzheimer’s disease, Parkinson’s disease, post-traumatic stress disorder, stroke, attention deficit hyperactivity disorder, autism, depression, schizophrenia and other disorders.

    Knowing what the master genes are could give scientists targets for new pharmaceuticals to treat brain diseases. Eventually, scientists might even be able to learn how to re-modify damaged genes to reduce the risk for diseases, and the finding could help researchers identify chemical compounds and foods that fight disease by repairing those genes.

    “We believe these master genes are responsible for traumatic brain injury adversely triggering changes in many other genes,” said Xia Yang, a senior author of the study and a UCLA associate professor of integrative biology and physiology.

    Genes have the potential to become any of several types of proteins, and traumatic brain injury can damage the master genes, which can then lead to damage of other genes.

    That process can happen in a couple of ways, said Yang, who is a member of UCLA’s Institute for Quantitative and Computational Biosciences. One is that the injury can ultimately lead the genes to produce proteins of irregular forms. Another is to change the number of expressed copies of a gene in each cell. Either change can prevent a gene from working properly. If a gene turns into the wrong form of protein, it could lead to Alzheimer’s disease, for example.

    “Very little is known about how people with brain trauma — like football players and soldiers — develop neurological disorders later in life,” said Fernando Gomez-Pinilla, a UCLA professor of neurosurgery and of integrative biology and physiology, and co-senior author of the new study. “We hope to learn much more about how this occurs.”

    The research appears in EBioMedicine, a journal published by Cell and The Lancet.

    The researchers trained 20 rats to escape from a maze. They then used a fluid to produce a concussion-like brain injury in 10 of the rats; the 10 others did not receive brain injuries. When the rats were placed in the maze again, those that had been injured took approximately 25 percent longer than the non-injured rats to solve it.

    To learn how the rats’ genes had changed in response to the brain injury, the researchers analyzed genes from five animals in each group. Specifically, they drew RNA from the hippocampus, which is the part of the brain that helps regulate learning and memory, and from leukocytes, white blood cells that play a key role in the immune system.

    In the rats that had sustained brain injuries, there was a core group of 268 genes in the hippocampus that the researchers found had been altered, and a core group of 1,215 genes in the leukocytes that they found to have been changed.

    “A surprise was how many major changes occurred to genes in the blood cells,” Yang said. “The changes in the brain were less surprising. It’s such a critical region, so it makes sense that when it’s damaged, it signals to the body that it’s under attack.”

    Nearly two dozen of the altered genes are present in both the hippocampus and the blood, which presents the possibility that scientists could develop a gene-based blood test to determine whether a brain injury has occurred, and that measuring some of those genes could help doctors predict whether a person is likely to develop Alzheimer’s or other disorders. The research could also lead to a better way to diagnose mild traumatic brain injury.

    More than 100 of the genes that changed after the brain injury have counterparts in humans that have been linked to neurological and psychiatric disorders, the researchers report. For example, 16 of the genes affected in the rats have analogs in humans, and those genes are linked to a predisposition for Alzheimer’s, the study reports. The researchers also found that four of the affected genes in the hippocampus and one in leukocytes are similar to genes in humans that are linked to PTSD.

    Yang said the study not only indicated which genes are affected by traumatic brain injury and linked to serious disease, but also might point to the genes that govern metabolism, cell communication and inflammation — which might make them the best targets for new treatments for brain disorders.

    The researchers now are studying some of the master genes to determine whether modifying them also causes changes in large numbers of other genes. If so, the master genes would be even more promising as targets for new treatments. They also plan to study the phenomenon in people who have suffered traumatic brain injury.

    In a 2016 study, Yang, Gomez-Pinilla and colleagues reported that hundreds of genes can be damaged by fructose and that an omega-3 fatty acid called docosahexaenoic acid, or DHA, seems to reverse the harmful changes produced by fructose. One of the genes they identified in that study, Fmod, also was among the master regulator genes identified in the new research.

    Not everyone with traumatic brain injuries develops the same diseases, but more severe injuries can damage more genes, said Gomez-Pinilla, who also is a member of UCLA’s Brain Injury Research Center.

     


  3. Rapid blood pressure drops in middle age linked to dementia in old age

    March 14, 2017 by Ashley

    From the Johns Hopkins University Bloomberg School of Public Health media release:

    Middle-aged people who experience temporary blood pressure drops that often cause dizziness upon standing up may be at an increased risk of developing cognitive decline and dementia 20 years later, new Johns Hopkins Bloomberg School of Public Health research suggests.

    The findings, being presented March 10 at the American Heart Association’s EPI|LIFESTYLE 2017 Scientific Sessions in Portland, Ore., suggest that these temporary episodes — known as orthostatic hypotension — may cause lasting damage, possibly because they reduce needed blood flow to the brain. Previous research has suggested a connection between orthostatic hypotension and cognitive decline in older people, but this appears to be the first to look at long-term associations.

    “Even though these episodes are fleeting, they may have impacts that are long lasting,” says study leader Andreea Rawlings, PhD, MS, a post-doctoral researcher in the Department of Epidemiology at the Bloomberg School. “We found that those people who suffered from orthostatic hypotension in middle age were 40 percent more likely to develop dementia than those who did not. It’s a significant finding and we need to better understand just what is happening.”

    An estimated four million to five million Americans currently have dementia and, as the population ages, that number is only expected to grow. There currently is no treatment and no cure for the condition.

    For the study, the researchers analyzed data from the Atherosclerosis Risk in Communities (ARIC) cohort, a study of 15,792 residents in four communities in the United States, who were between the ages of 45 and 64 when the study began in 1987. For this study, they focused on the 11,503 participants at visit one who had no history of coronary heart disease or stroke. After 20 minutes lying down, researchers took the participants’ blood pressure upon standing. Orthostatic hypotension was defined as a drop of 20 mmHg or more in systolic blood pressure or 10 mmHg or more in diastolic blood pressure. Roughly six percent of participants, or 703 people, met the definition.

    These participants, who were on average 54 years old upon enrolling in the study, continued to be followed over the next 20 or more years. People with orthostatic hypotension at the first visit were 40 percent more likely to develop dementia than those who did not have it. They had 15 percent more cognitive decline.

    Rawlings says it is not possible to tease out for certain whether the orthostatic hypotension was an indicator of some other underlying disease or whether the drop in blood pressure itself is the cause, though it is likely that the reduction in blood flow to the brain, however temporary, could have lasting consequences.

    It also wasn’t clear, she says, whether these participants had repeated problems with orthostatic hypotension over many years or whether they had just a brief episode of orthostatic hypotension at the original enrollment visit, as patients were not retested over time.

    “Identifying risk factors for cognitive decline and dementia is important for understanding disease progression, and being able to identify those most at risk gives us possible strategies for prevention and intervention,” Rawlings says. “This is one of those factors worth more investigation.”


  4. Benzodiazepines, related drugs increase stroke risk among persons with Alzheimer’s disease

    January 25, 2017 by Ashley

    From the University of Eastern Finland media release:

    memory lossThe use of benzodiazepines and benzodiazepine-like drugs was associated with a 20 per cent increased risk of stroke among persons with Alzheimer’s disease, shows a recent study from the University of Eastern Finland. Benzodiazepines were associated with a similar risk of stroke as benzodiazepine-like drugs.

    The use of benzodiazepines and benzodiazepine-like drugs was associated with an increased risk of any stroke and ischemic stroke, whereas the association with hemorrhagic stroke was not significant. However, due to the small number of hemorrhagic stroke events in the study population, the possibility of such an association cannot be excluded. The findings are important, as benzodiazepines and benzodiazepine-like drugs were not previously known to predispose to strokes or other cerebrovascular events. Cardiovascular risk factors were taken into account in the analysis and they did not explain the association.

    The findings encourage a careful consideration of the use of benzodiazepines and benzodiazepine-like drugs among persons with Alzheimer’s disease, as stroke is one of the leading causes of death in this population group. Earlier, the researchers have also shown that these drugs are associated with an increased risk of hip fracture.

    The study was based on data from a nationwide register-based study (MEDALZ) conducted at the University of Eastern Finland in 2005-2011. The study population included 45,050 persons diagnosed with Alzheimer’s disease, and 22 per cent of them started using benzodiazepines or benzodiazepine-like drugs.

    The findings were published in International Clinical Psychopharmacology.


  5. The lasting effects of ministrokes may contribute to dementia

    January 24, 2017 by Ashley

    From the Medical University of South Carolina media release:

    hospital emergency signEvidence overwhelmingly supports a link between cognitive decline and cerebrovascular diseases such as atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy.

    Not only do individuals with cerebrovascular diseases have a much higher incidence of cortical microinfarcts (mini-strokes), but post-mortem histological and in vivo radiological studies also find that the burden of microinfarcts is significantly greater among people with vascular cognitive impairment and dementia (VCID) than in age-matched, non-demented individuals.

    Until now, the mechanisms by which these miniscule lesions (~0.05 to 3 millimeters in diameter) contribute to cognitive deficits including dementia have been poorly understood.

    Findings from a recent study by investigators at the Medical University of South Carolina (MUSC) provide crucial information for better understanding the impact of microinfarcts, showing that the functional deficits caused by a single microinfarct can affect a larger area of brain tissue and last longer than was previously thought to be the case.

    The functional effects of microinfarcts are extremely difficult to study. Not only are most microinfarcts difficult to detect with standard neuroimaging techniques, mismatches between in vivo functional data and post-mortem histological evidence make it nearly impossible to connect microinfarcts to the timeline of cognitive decline.

    These infarcts are so small and unpredictable, we just haven’t had good tools to detect them while the person was still alive,” said Andy Shih, Ph.D., Assistant Professor of Neurosciences and senior author on the article. “So, until now, we basically just had post-mortem snapshots of these infarcts at the end of the dementia battle as well as measures of the person’s cognitive decline, which might have been taken years before the brain became available for study.”

    Intrigued by the mounting evidence linking cognitive decline and microinfarct burden, Shih’s group hypothesized that microinfarcts might disrupt brain function beyond what was visible by histology or magnetic resonance imaging (MRI).

    Even though a person may experience hundreds of thousands of microinfarcts in their lifetime, each event is extremely small and thought to resolve in a matter of days,” said Shih. “It’s been estimated that, overall, microinfarcts affect less than 2% of the entire human brain. But those estimates of tissue loss are based only on the ‘core’ of the microinfarct, the area of dead or dying tissue that we can see in routine, post-mortem, histological stains.”

    To investigate their theory of broader impacts, the team developed a mouse model so that they could examine the effects of individual cortical microinfarcts on surrounding tissue function in vivo over several weeks post-event. “We needed a preclinical model to create very predictable lesions that we could follow over time,” said Shih. “Also, we needed to be able to obtain readouts of brain activity that were consistent over time.”

    The team used photothrombosis to occlude a single arteriole in the barrel cortex of mice fitted with cranial windows. They then compared functional readouts of sensory-evoked brain activity, indicated by activity-dependent c-Fos expression or in vivo two-photon imaging of single vessel hemodynamic responses, to the location of the microinfarct core.

    Post-mortem, c-Fos immunostaining revealed that an area estimated to be at least 12-times greater in volume than the microinfarct core had been affected by the event. Furthermore, in vivo, two-photon imaging of single vessel, sensory-evoked hemodynamics found that neuronal activity across the affected tissue area remained partially depressed for 14 to 17 days after the microinfarct.

    Together, these data indicate that functional deficits caused by a single microinfarct occur across a much larger area of viable peri-lesional tissue than was previously understood and that the resulting deficits are much longer-lasting.

    I knew larger strokes could have distant effects, but I was surprised that something of this scale could have such a large effect,” said Shih.

    The duration of effect from a single microinfarct was also a surprise for Shih’s team. “The MRI signal increased and then went away as we’d expected, but we were surprised on autopsy to see that there was still lots going on — tissue damage and neuroinflammation,” Shih explained. “Even after three weeks the neurally evoked blood flow responses had only partially recovered. So, that means a microinfarct can come and go and you can see it briefly with MRI but it leaves a lasting impression on brain function-possibly for months.”

    Importantly, a person with VCID is likely to experience other microinfarcts during this recovery time. Furthermore, these tiny infarcts occur not only in the brain’s grey matter, where this study was conducted, but also in the white matter, which sends messages from one part of the brain to another.

    “Over time, after you have a lot of microinfarcts, there may be enough accumulated damage in the brain’s circuitry to equal the impact of a larger event,” said Shih.

    According to Shih, one of the most important messages from this study is that conventional methods used in clinical trials do not reveal the entire impact that microinfarcts have on brain function. He hopes that his team’s contribution to illuminating microinfarct pathology will help inform MRI interpretation in humans and help researchers better explain some of the relationships that they see in clinical studies.

    These findings might also lead to new preventive protocols. “On a clinical level, maybe it’s a situation where therapeutics can play a bigger role. Maybe drugs that we already have can mitigate the cumulative damage of microinfarcts,” speculated Shih. “The neuro-protective idea hasn’t flown very far for acute stroke, in part, because the window of time for protecting the brain from stroke damage is very narrow. But, for microinfarcts, you don’t have to know exactly when they occur. If an MRI shows a person is at high risk for microinfarcts, maybe one day we can put them on a drug for a while to reduce the impacts of these lesions.”


  6. Living near major traffic linked to higher risk of dementia

    January 13, 2017 by Ashley

    From the Public Health Ontario media release:

    night trafficPeople who live close to high-traffic roadways face a higher risk of developing dementia than those who live further away, new research from Public Health Ontario (PHO) and the Institute for Clinical Evaluative Sciences (ICES) has found.

    Led by PHO and ICES scientists, the study found that people who lived within 50 metres of high-traffic roads had a seven per cent higher likelihood of developing dementia compared to those who lived more than 300 meters away from busy roads.

    Published in The Lancet, the researchers examined records of more than 6.5 million Ontario residents aged 20-85 to investigate the correlation between living close to major roads and dementia, Parkinson’s disease and multiple sclerosis.

    Scientists identified 243,611 cases of dementia, 31,577 cases of Parkinson’s disease, and 9,247 cases of multiple sclerosis in Ontario between 2001 and 2012. In addition, they mapped individuals’ proximity to major roadways using the postal code of their residence. The findings indicate that living close to major roads increased the risk of developing dementia, but not Parkinson’s disease or multiple sclerosis, two other major neurological disorders.

    “Little is known in current research about how to reduce the risk of dementia. Our findings show the closer you live to roads with heavy day-to-day traffic, the greater the risk of developing dementia. With our widespread exposure to traffic and the greater tendency for people to live in cities these days, this has serious public health implications,” says Dr. Hong Chen, environmental and occupational health scientist at PHO and an adjunct scientist at ICES. Dr. Chen is lead author on the paper titled Living Near Major Roads and the Incidence of Dementia, Parkinson’s Disease, and Multiple Sclerosis: A Population-based Cohort Study.

    Our study is the first in Canada to suggest that pollutants from heavy, day-to-day traffic are linked to dementia. We know from previous research that air pollutants can get into the blood stream and lead to inflammation, which is linked with cardiovascular disease and possibly other conditions such as diabetes. This study suggests air pollutants that can get into the brain via the blood stream can lead to neurological problems,” says Dr. Ray Copes, chief of environmental and occupational health at PHO and an author on the paper.

    As urban centres become more densely populated and more congested with vehicles on major roads, Dr. Copes suggests the findings of this paper could be used to help inform municipal land use decisions as well as building design to take into account air pollution factors and the impact on residents.

    This research was conducted in collaboration with scientists from the University of Toronto, Carleton University, Dalhousie University, Oregon State University, and Health Canada. The study was funded by Health Canada.

    Key findings:

    • Using data held at ICES, the researchers examined records of more than 6.5 million Ontario residents, aged 20-85, and mapped them according to residential postal codes five years before the study started.
    • Between 2001 and 2012, 243,611 cases of dementia, 31,577 cases of Parkinson’s disease, and 9,247 cases of multiple sclerosis were identified in Ontario.
    • People who lived within 50 metres of high-traffic roads had a seven per cent higher likelihood of dementia than those who lived more 300 meters away from busy roads.
    • The increase in the risk of developing dementia went down to four per cent if people lived 50-100 metres from major traffic, and to two per cent if they lived within 101-200 metres. At over 200 metres, there was no elevated risk of dementia.
    • There was no correlation between major traffic proximity and Parkinson’s disease or multiple sclerosis.

     


  7. Active-duty military find PTSD relief through individual cognitive therapy

    November 29, 2016 by Ashley

    From the Duke University Medical Center media release:

    military_soldierAlthough both group and individual therapy can ease post-traumatic stress disorder (PTSD) symptoms in active-duty military service members, individual therapy relieved PTSD symptoms better and quicker, according to a study led by a Duke University School of Medicine researcher.

    The randomized clinical trial is the largest to date to examine an evidence-based treatment for active-duty military service members, with 268 participants from the U.S. Army’s Fort Hood in Killeen, Texas. Findings will be published Nov. 23 in JAMA Psychiatry.

    The study analyzed the effectiveness of six weeks of Cognitive Processing Therapy (CPT), and found that nearly half the participants in one-on-one therapy improved so much they no longer carried a PTSD diagnosis. Almost 40 percent of the participants in group sessions also dropped their PTSD diagnoses after six weeks.

    For some of the participants, you can see a change just by looking at them — as though they have been unburdened,” said Patricia Resick, Ph.D., the study’s lead author, who developed CPT in the 1980s for victims of rape and other interpersonal trauma and is now a professor of psychiatry and behavioral sciences at the Duke University School of Medicine.

    “Some people think you have to go to therapy for years to address PTSD, but in this large-scale clinical trial with CPT, we saw a large percentage of patients show significant improvements and even recover from PTSD in a matter of weeks,” Resick said.

    CPT examines how an individual thinks about a traumatic event and how that affects their emotions, Resick said.

    “We look at what people have been saying to themselves about the trauma, which in people with PTSD can be distorted,” Resick said. “Many of them think there’s something they could have done differently to prevent the trauma. We teach them how to examine their thoughts and feel their natural emotions instead of feelings, such as guilt or blame that may result from distorted thinking. We go back and look at the evidence. Once they think in a more balanced, factual way, their emotions and symptoms of PTSD subside.”

    To measure effectiveness in active-duty military members, the trial was established through STRONG STAR Consortium, a multi-institutional initiative to develop and evaluate effective prevention, detection and treatment of combat-related PTSD. The consortium is funded by the U.S. Department of Defense.

    “Cognitive-behavioral therapies such as CPT and Prolonged Exposure therapy are the leading treatments for PTSD, with the most scientific support for their effectiveness,” said Alan Peterson, Ph.D., director of the STRONG STAR Consortium and professor of psychiatry at the University of Texas Health Science Center San Antonio.

    However, both were developed primarily for civilians, and until the STRONG STAR Consortium was developed, they had never been evaluated in clinical trials with an active-duty military population,” said Peterson, who is also a retired lieutenant colonel of the U.S. Air Force. “This study shows that CPT is effective, but it still needs to be adapted and tailored in ways that increase its effectiveness with combat-related PTSD so that more patients can fully recover.”

    About half of the participants were assigned to group therapy, attending 90-minute sessions twice a week for six weeks. The other half met one-on-one with a therapist for 60-minute sessions twice a week for six weeks.

    Independent evaluators used standard PTSD diagnostic tools to measure the severity of PTSD and associated conditions such as depression and suicidal thoughts. The participants were evaluated before and during treatment, with a follow-up six months after the treatment was over.

    For all participants, PTSD-related symptoms such as nightmares, intrusive thoughts or being easily startled improved. Overall, about 50 percent of participants experienced such improvement that they no longer met the criteria for a PTSD diagnosis, although many still had some symptoms, particularly trouble sleeping, Resick said.

    Those who attended individual therapy saw more significant improvements in the severity of their PTSD symptoms and the improvements were seen more quickly, Resick said.

    The study also showed that whether subjects received group or individual therapy, they had equal reductions in depression and suicidal thinking. These results continued through a six-month follow-up.

    The findings are based on the total 268 participants who enrolled and intended to complete the full six-week program. Overall results include about 9 percent of participants who did not begin treatment due to military deployment or other reasons, and participants who received fewer than 12 sessions (full details included in manuscript).

    The findings, although encouraging, show that many participants still had lingering symptoms after six weeks of treatment, and about half retained their PTSD diagnosis. Further research will allow researchers to refine the therapy, considering any specific adjustments for active-duty service members such as varying the number of weeks patients would participate. Researchers with the STRONG STAR Consortium will also expand on the research by evaluating the roles of substance abuse and traumatic brain injury on patients’ outcomes.


  8. Researchers use video gamelike test to study learning and recovery in stroke patients

    October 31, 2016 by Ashley

    From the Johns Hopkins Medicine media release:

    hospital stayA robotic arm and a virtual game were essential tools in a new study from researchers at Johns Hopkins Medicine. The study results suggest that while training doesn’t change neurological repair in chronic stroke patients, it can indeed help such patients learn new motor skills and achieve more independence in their daily lives.

    A report on the work is published in the journal Neurorehabilitation and Neural Repair on Oct. 27.

    “What we found is that physical rehab is not going to change the weakness caused by damaged brain cells in chronic patients, but it is going to change how well they can perform certain tasks, which can have a huge impact on a patient’s daily life,” says Pablo Celnik, M.D., director of the Department of Physical Medicine and Rehabilitation at Johns Hopkins.

    Brain damage from strokes occurs when the blood supply to the brain is blocked (ischemic stroke) or a blood vessel feeding brain tissue ruptures (hemorrhagic stroke). Depending on the extent of the stroke, the damage can cause partial or total paralysis, affecting motor function, balance, speech, sensation and other physical activities. Chronic stroke patients are those whose physical impairments persist more than six months after the stroke. Rehabilitation specialists measure the damage using the Fugl-Meyer Assessment (FMA), which measures the neurological damage wrought by a stroke on a scale from zero to 66.

    For the new study, the investigators recruited 10 chronic stroke patients with FMA scores of ?50 out of 66 and categorized them as having “mild to moderate” functional deficits for the purposes of the study, and 10 other patients with FMA scores of <50 out of 66 and categorized them as having “moderate to severe” impairment. A third group of 10 able-bodied participants served as a control group.

    All of the study participants were trained to control a simple video game using a using a robotic piece of equipment that held their dominant arm at 90 degrees from their bodies. This eliminated gravity as a burden for those whose arms were weakened by their strokes. The subjects were then taught to use the muscles around their elbow to move a cursor across a screen into small target windows.

    Participants’ performance in the game was measured during training sessions and skill assessment trials. A pre-training skill assessment was conducted to get a baseline from which to measure improvement. Participants were asked to move the cursor through the windows in time with a metronome and completed nine blocks of 10 trials at various speeds — 24, 30, 38, 45, 60, 80, 100, 110 and 120 beats per minute. The metronome prevented participants from slowing down to improve their accuracy, so the only way to show improvement was by becoming more skilled at the task.

    The next phase of the experiment had participants attend 30-minute training sessions for four consecutive days. They were asked to complete five blocks of 30 trials, all at their own pace, and were encouraged to improve their speed and accuracy in each consecutive block. Following the training sessions, participants’ skill levels were tested again in another skill assessment.

    Results showed that while each group’s skill level improved by the end of the training, those with greater motor impairment still demonstrated less skill in both the pre- and post-training assessments. All participants reached a plateau in their improvement around experimental days three and four.

    However, the study showed that there was considerable overlap between the post-training performance of the stroke patients and the pre-training performance of groups with less impairment. “When you look at the data, the post-training mild-to-moderate group is indistinguishable from the pre-training control group. And the same was true for post-training scores of those in the moderate-to-severe group and the mild-to-moderate group,” says Robert Hardwick, Ph.D., postdoctoral fellow in the Department of Neurology at the Johns Hopkins University School of Medicine.

    This is good news for patients because it means that even when there is little likelihood of further neurological recovery, it means I can still teach them new tasks through training,” says Celnik. “What is important is to not create false expectations of neurological recovery, while at the same time being hopeful that patients can learn within the boundaries of their neurological deficit to improve their lives.”

    According to the World Health Organization, 15 million people worldwide suffer a stroke each year. An estimated 5 million die, and another 5 million are left with lasting motor impairment. Celnik cautions that this study only included chronic stroke patients and that their future research plans include conducting similar studies in acute stroke patients — those within three months of the stroke — which could yield different results. “Maybe there is a different impact of training in the earlier stages of stroke damage,” says Celnik.


  9. Scientists identify new lead in search for Parkinson’s cure

    October 5, 2016 by Ashley

    From the Iowa State University media release:

    walker parkinsonsRecently published research from Iowa State University may hint at a new treatment for Parkinson’s disease.

    In a paper published in the academic journal Nature Communications, ISU scientists identified a protein called Prokineticin-2 (PK2) that may protect brain cells and is expressed with greater frequency in the early stages of Parkinson’s disease.

    The neurons use PK2 to cope with stress. It’s an in-built protective mechanism,” said Anumantha Kanthasamy, a Clarence Hartley Covault Distinguished Professor in veterinary medicine, the Eugene and Linda Lloyd Endowed Chair of Neurotoxicology, and chair of biomedical sciences at Iowa State. Kanthasamy, one of the paper’s lead authors, has been working to understand the complex mechanisms of Parkinson’s and searching for a cure for the past two decades.

    Prokineticin-2 stimulates the neurons to produce more mitochondria, the part of the cell that produces energy. The resulting improved energy production helps neurons withstand the ravages of the disease, which is a neurological disorder that results in insufficient levels of dopamine in the brain.

    Parkinson’s disease is a progressive disorder that takes years to develop. A better understanding of Prokineticin-2 could turn up a means of slowing development of the disease or lead to new therapies, Kanthasamy said. For instance, there may be ways to stimulate more production of the protein or protein analogs to bind with its receptors on neurons, he said.

    The research team took a multidisciplinary and integrated approach to studying Parkinson’s disease. The study was funded by a grant from the National Institutes of Health to Kanthasamy and Arthi Kanthasamy, a professor of biomedical sciences and Anumantha’s spouse. Six graduate students in Kanthasamy’s lab also contributed to the study, including co-first authors Richard Gordon and Matthew Neal, as well as researchers at other institutions.

    The scientists studied cultured brain cells, a rodent model and post-mortem human brains to track changes brought on by Parkinson’s disease, and they confirmed a high expression of Prokineticin-2 in each facet of the study.

    It was this team effort that resulted in a comprehensive finding, Arthi Kanthasamy noted.

    The discovery prompted the research team to investigate more thoroughly.

    “Of the thousands and thousands of factors we tracked in our experiments, why was this protein expressed so highly?” Arthi Kanthasamy said.

    Finding the answer to that question poses a challenge that will take time to overcome, but the potential appears to be significant, she said.


  10. Breakthrough in brain cancer research

    June 30, 2016 by Ashley

    From the Newcastle University media release:

    brain scansScientists at Newcastle University, UK, have made a pioneering breakthrough in the understanding of how a fatal brain tumour grows — which could lead to improved treatments for patients.

    Experts have found cells within the malignant brain tumour, glioma, rely on fats to fuel growth. This contradicts previous scientific belief that tumour cells require mainly sugars to make energy.

    Glioma is the most common form of primary malignant brain tumour in adults, with approximately four cases per 100,000 people each year. Gliomas remain one of the hardest to treat cancers.

    This new discovery provides a unique view of brain cancer cell biology which has significant implications for understanding the behaviour of tumours and improve treatments for this condition.

    The study made use of tumour tissue donated by patients undergoing surgery, as well as mouse models of the disease.

    Findings of the research are published online today in the journal, Neuro-Oncology.

    Dr Elizabeth Stoll, from Newcastle University’s Institute of Neuroscience, is lead author of the ground-breaking study.

    She said: “Patients with malignant glioma currently receive a poor prognosis, and new interventions are desperately needed to increase the survival and quality of life for patients with the condition.

    “Our results provide new insight into the fundamental biochemistry of cancer cells, with exciting implications for patients in the future.

    Most cells within the adult brain require sugars to produce energy and sustain function. Interestingly, we have discovered that malignant glioma cells have a completely different metabolic strategy as they actually prefer to break down fats to make energy.

    “Our finding provides a new understanding of brain tumour biology, and a new potential drug target for fighting this type of cancer.”

    In the study, scientists showed that glioma cells grow more slowly if they are treated with a drug, known as etomoxir, which prevents the cells from making energy with fatty acids.

    This discovery provides initial evidence for pursuing new therapeutic avenues to target fatty-acid metabolism in the clinical treatment of brain tumours to slow the progression of the disease.

    The team highlight that this study does not address whether nutrition or diet influence tumour growth.

    Dr Stoll said: “We tested etomoxir in our animal model, and showed that systemic doses of this drug slow glioma growth, prolonging median survival time by 17%.

    “These results provide a novel drug target which could aid in the clinical treatment of this disease for patients in the future.”

    Stem cells were isolated from brains of mice and mutated to transform them into cancer cells. These mutations were similar to those that normally accumulate to form glioma tumours in people.

    The malignant cells were then implanted into mice of the same genetic background as the donor mice, allowing the team to assess the speed of growth of the tumour.

    Dr Stoll and her team hope to carry out future studies to develop the drug with clinical partners, so that glioma patients may benefit from this research in the coming years.