Posts tagged stroke
Posts tagged stroke
Using a novel stroke rehabilitation device that converts an individual’s thoughts to electrical impulses to move upper extremities, stroke patients reported improvements in their motor function and ability to perform activities of daily living. Results of the study were presented today at the annual meeting of the Radiological Society of North America (RSNA).
"Each year, nearly 800,000 people suffer a new or recurrent stroke in the United States, and 50 percent of those have some degree of upper extremity disability," said Vivek Prabhakaran, M.D., Ph.D., director of functional neuroimaging in radiology at the University of Wisconsin-Madison. "Rehabilitation sessions with our device allow patients to achieve an additional level of recovery and a higher quality of life."
Dr. Prabhakaran, along with co-principal investigator Justin Williams, Ph.D., and a multidisciplinary team, built the new rehabilitation device by pairing a functional electrical stimulation (FES) system, which is currently used to help stroke patients recover limb function, and a brain control interface (BCI), which provides a direct communication pathway between the brain and this peripheral stimulation device.
In an FES system, electrical currents are used to activate nerves in paralyzed extremities. Using a computer and an electrode cap placed on the head, the new BCI-FES device (called the Closed-Loop Neural Activity-Triggered Stroke Rehabilitation Device) interprets electrical impulses from the brain and transmits the information to the FES.
"FES is a passive technique in that the electrical impulses move the patients’ extremities for them," Dr. Prabhakaran said. "When a patient using our device is asked to imagine or attempt to move his or her hand, the BCI translates that brain activity to a signal that triggers the FES. Our system adds an active component to the rehabilitation by linking brain activity to the peripheral stimulation device, which gives the patients direct control over their movement."
The Wisconsin team conducted a small clinical trial of their rehabilitation device, enlisting eight patients with one hand affected by stroke. The patients were also able to serve as a control group by using their normal, unaffected hand. Patients in the study represented a wide range of stroke severity and amount of time elapsed since the stroke occurred. Despite having received standard rehabilitative care, the patients had varying degrees of residual motor deficits in their upper extremities. Each underwent nine to 15 rehabilitation sessions of two to three hours with the new device over a period of three to six weeks.
The patients also underwent functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) before, at the mid-point of, at the end of, and one month following the rehabilitation period. fMRI is able to show which areas of the brain are activated while the patient performs a task, and DTI reveals the integrity of fibers within the white matter that connects the brain’s functional areas.
Patients who suffered a stroke of moderate severity realized the greatest improvements to motor function following the rehabilitation sessions. Patients diagnosed with mild and severe strokes reported improved ability to complete activities of daily living following rehabilitation.
Dr. Prabhakaran said the results captured throughout the rehabilitation process—specifically the ratio of hemispheric involvement of motor areas—related well to the behavioral changes observed in patients. A comparison of pre-rehabilitation and post-rehabilitation fMRI results revealed reorganization in the regions of the brain responsible for motor function. DTI results over the course of the rehabilitation period revealed a gradual strengthening of the integrity of the fiber tracts.
"Our hope is that this device not only shortens rehabilitation time for stroke patients, but also that it brings a higher level of recovery than is achievable with the current standard of care," Dr. Prabhakaran said. "We believe brain imaging will be helpful in both planning and tracking a stroke patient’s therapy, as well as learning more about neuroplastic changes during recovery."
With right-handed people, it is positioned in the left side of the brain; left-handed people have it (usually) in the right side: the location of speech production has been known for quite some time. But it is not that simple, states psychologist Gesa Hartwigsen, Professor at Kiel University. In her current scientific publication, published in the magazine Proceedings of the National Academy of Science of the USA (PNAS), she investigates which areas in the brain really are in charge of speech, and how these interact. Her findings are supposed to help patients who have speech production problems or aphasia following a stroke.
Comprehending & Speaking
Gesa Hartwigsen and her team started by analysing speech production. They let healthy right-handed test persons listen to words, which they should then repeat. “These were pseudo words such as `beudo`. In German, they don’t have any associated meaning. Therefore, when hearing and repeating these words, no areas of the brain that had a connection to the meaning of what had been heard were activated”, said Hartwigsen.
The psychologist applies a combination of non-invasive methods (fMRI– functional magnetic resonance imaging and TMS – transcranial magnetic stimulation) to deduce what happens in the brain during the test. “We thus proved that the left hemisphere, as expected, was activated during speech production, while the right hemisphere did not actively contribute to language function”, explains Hartwigsen. This is the regular functionality within a healthy brain. From these results as well as others, scientists had up to now deduced that the right hemisphere did not contribute to speech production in the healthy system and was therefore suppressed.
Interfering & Measuring
With a second test, the Kiel University scientists simulated a dysfunction in the brain comparable to a stroke. A magnetic coil transmits a current pulse that interrupts the function of the area responsible for producing speech (Broca’s Area) in the left hemisphere. This completely harmless method influences the speech production of the volunteers for about 30 to 45 minutes. “During this period, the ability to listen and repeat was tested again. While we observed a suppressed activity in the left hemisphere during repeating, with some test persons taking longer to repeat the pseudo words, we also found unexpected activities in the right hemisphere”, reports Hartwigsen.
The right hemisphere showed increased activity during pseudo word repetition. The more the activity in the right Borca’s Area increased, the faster the volunteers were able to solve their speech tests. The right hemisphere also increased its facilitatory influence on the right hemisphere, a finding that was not observed prior to the TMS-induced lesion. “This reaction lends further support to the notion that the right hemisphere area reacts to the dysfunction of the left hemisphere and tries to compensate for the lesion.” Does the right hemisphere have a supporting influence and does it play an active role in speech production? So far, the common opinion was that it does not.
Result & Outlook
The findings of Gesa Hartwigsen and her team show an interaction of both hemispheres during speech repetition. When the left hemisphere is suppressed for example by a stroke, the right hemisphere could actively facilitate speech production. “By stimulating the right hemisphere, it could be possible to support speech recovery”, speculates the scientist. Here, timing would be very important. “Right after a stroke, we could support the right hemisphere. But when the remaining areas of the left hemisphere are ready to do their work again, it might be more helpful if the right hemisphere was suppressed. During this phase, we could stimulate the left hemisphere instead. The correct timing can therefore be crucial for recovery of speech after a stroke.”
In collaboration with the Department of Neurology at Kiel University, a stroke specialist from Leipzig and doctoral students of Medicine and Psychology, Gesa Hartwigsen has started a follow-up study on the recent publication. “We would like to find out more about the collaboration of the hemispheres and the right timing in helping stroke patients to recover”, says Hartwigsen. Her field of research is fairly new within the cognitive neuroscience. Nevertheless, she is positive that it will offer practical help in the form of concrete therapies within the next ten to fifteen years.
Researchers at The Ohio State University Wexner Medical Center have developed a therapeutic at-home gaming program for stroke patients who experience motor weakness affecting 80 percent of survivors.
Hemiparesis affects 325,000 individuals each year, according to the National Stroke Association. It is defined as weakness or the inability to move one side of the body, and can be debilitating as it impacts everyday functions such as eating, dressing or grabbing objects.
Constraint-induced movement therapy (CI therapy) is an intense treatment recommended for stroke survivors, and improves motor function, as well as the use of impaired upper extremities. However, less than 1 percent of those affected by hemiparesis receives the beneficial therapy.
“Lack of access, transportation and cost are contributing barriers to receiving CI therapy. To address this disparity, our team developed a 3D gaming system to deliver CI therapy to patients in their homes,” said Lynne Gauthier, assistant professor of physical medicine and rehabilitation in Ohio State’s College of Medicine.
Gauthier, also principal investigator of the study and a neuroscientist, is collaborating with a multi-disciplinary team comprised of clinicians, computer scientists, an electrical engineer and a biomechanist to design an innovative video game incorporating effective ingredients CI therapy.
For a combined 30 hours over the course of two weeks, the patient-gamer is immersed in a river canyon environment, where he or she receives engaging high repetition motor practice targeting the affected hand and arm. Various game scenarios promote movements that challenge the stroke survivor and are beneficial to recovery. Some examples include: rowing and paddling down a river, swatting away bats inside a cave, grabbing bottles from the water, fishing, avoiding rocks in the rapids, catching parachutes containing supplies and steering to capture treasure chests. Throughout the intensive training schedule, the participant wears a padded mitt on the less affected hand for 10 hours daily, to promote the use of the more affected hand.
To ensure that motor gains made through the game carry over to daily life, the game encourages participants to reflect on their daily use of the weaker arm and engages the gamer in additional problem-solving ways of using the weaker arm for daily activities.
“This novel model of therapy has shown positive results for individuals who have played the game. Gains in motor speed, as measured by the Wolf Motor Function Test, rival those made through traditional CI therapy,” said Gauthier. “It provides intense high quality motor practice for patients, in their own homes. Patients have reported they have more motivation, time goes by quicker and the challenges are exciting and not so tedious.”
Gauthier said that, if this initial trial demonstrates sufficient evidence of efficacy in stroke survivors, future expansion of gaming CI therapy is possible for other patients with traumatic brain injury, cerebral palsy and multiple sclerosis.
A study led by researchers at The University of Texas Health Science Center at Houston (UTHealth) showed that a hands-free ultrasound device combined with a clot-busting drug was safe for ischemic stroke patients.
The results of the phase II pilot study were reported today in the American Heart Association journal Stroke. Lead author is Andrew D. Barreto, M.D., assistant professor of neurology in the Stroke Program at the UTHealth Medical School. Principal investigator is James C. Grotta, M.D., professor and chair of the Department of Neurology at the UTHealth Medical School, the Roy M. & Phyllis Gough Huffington Distinguished Chair and co-director of the Mischer Neuroscience Institute at Memorial Hermann-Texas Medical Center.
The device, which uses UTHealth technology licensed to Cerevast Therapeutics, Inc., is placed on the stroke patient’s head and delivers ultrasound to enhance the effectiveness of the clot-busting drug tissue plasminogen activator (tPA). Unlike the traditional hand-held ultrasound probe that’s aimed at a blood clot, the hands-free device used 18 separate probes and showers the deep areas of the brain where large blood clots cause severe strokes.
“Our goal is to open up more arteries in the brain and help stroke patients recover,” said Barreto, an attending physician at Mischer Neuroscience Institute. “This technology would have a significant impact on patients, families and society if we could improve outcomes by another 10 percent or more by adding ultrasound to patients who’ve already received tPA.”
In the first study of its kind, 20 moderately severe ischemic stroke patients (12 men and eight women, average age 63 years) received intravenous tPA up to 4.5 hours after symptoms occurred and two hours exposure to 2-MHz pulsed wave transcranial ultrasound.
Researchers reported that 13 (or 65 percent) patients either returned home or to rehabilitation 90 days after the combination treatment. After three months, five of the 20 patients had no disability from the stroke and one had slight disability.
An experimental drug called 3K3A-APC appears to reduce brain damage, eliminate brain hemorrhaging and improve motor skills in older stroke-afflicted mice and stroke-afflicted rats with comorbid conditions such as hypertension, according to a new study from Keck Medicine of USC.
The report, which appears online in the journal Stroke, provides additional evidence that 3K3A-APC may be used as a therapy for stroke in humans, either alone or in combination with the Food and Drug Administration (FDA)-approved clot-busting drug therapy known as tissue plasminogen activator (tPA). Clinical trials to test the drug’s efficacy in people experiencing acute ischemic stroke are expected to begin recruiting patients across the United States next year.
“Currently, tPA is the best treatment for stroke caused by a blocked artery, but it must be administered within three hours after stroke onset to be effective,” said Berislav Zlokovic, director of the Zilkha Neurogenetic Institute (ZNI) at the Keck School of Medicine of USC and the study’s lead investigator. “Because of this limited window, only a small fraction of those who suffer a stroke reach the hospital in time to be considered for tPA. Our studies show that 3K3A-APC extends tPA’s therapeutic window and counteracts tPA’s tendency to induce bleeding in the brains of animals having a stroke.”
Zlokovic is the scientific founder of ZZ Biotech, a Houston-based biotechnology company he co-founded with USC benefactor Selim Zilkha to develop biological treatments for stroke and other neurological ailments.
ZZ Biotech’s 3K3A-APC is a genetically engineered variant of the naturally occurring activated protein C (APC), which plays a role in the regulation of blood clotting and inflammation. 3K3A-APC has been shown to have a protective effect on the lining of blood vessels in rodent brains, which appears to help prevent bleeding caused by tPA.
In collaboration with Cedars-Sinai Medical Center and The Scripps Research Institute, Zlokovic and his team gave tPA — alone and in combination with 3K3A-APC — to mature female mice and male hypertensive rats four hours after stroke. They also gave 3K3A-APC in regular intervals up to seven days after stroke. The researchers measured the amount of brain damage, bleeding and motor ability of the rodents up to four weeks after stroke.
The researchers found that, under those conditions, tPA therapy alone caused bleeding in the brain and did not reduce brain damage or improve motor ability when compared to the control. The combination of tPA and 3K3A-APC, however, reduced brain damage by more than half, eliminated tPA-induced bleeding and significantly improved motor ability.
“Scientists all around the globe are studying potential stroke therapies, but very few have the robust preclinical data package that 3K3A-APC has,” said Kent Pryor, ZZ Biotech’s chief operating officer. “The results from Dr. Zlokovic’s studies have been very promising.”
Zlokovic’s team previously reported similar results in young, healthy male rodents. A Phase 1 trial testing the safety of 3K3A-APC in healthy human volunteers, led by study co-author Patrick D. Lyden of Cedars-Sinai concluded in February.
“We now have opened an investigational new drug application at the FDA to conduct a Phase 2 clinical trial of 3K3A-APC in patients experiencing acute ischemic stroke,” said Joe Romano, CEO and president of ZZ Biotech. “We are excited to see 3K3A-APC move from healthy volunteers to real patients suffering from this terrible disease.”
Johns Hopkins researchers, working with mice, say they have identified a chemical compound that reduces the risk of dangerous, potentially stroke-causing blood vessel spasms that often occur after the rupture of a bulging vessel in the brain.
They say their findings offer clues about the biological mechanisms that cause vasospasm, or constriction of blood vessels that reduces oxygen flow to the brain, as well as potential means of treating the serious condition in humans.
When an aneurysm — essentially a blister-like bulge in the wall of a blood vessel — bursts, blood spills into the fluid-filled space that cushions the brain inside the skull. If a patient survives a ruptured aneurysm, between 20 and 40 percent of the time, this brain bleed, called a subarachnoid hemorrhage, will lead to an ischemic stroke within four to 21 days, even when the aneurysm is surgically clipped.
“We’re a long way from applying this to humans, but it’s a good start,” says Johns Hopkins neurosurgery resident Tomas Garzon-Muvdi, M.D., M.Sc., one of the authors of the study led by Rafael J. Tamargo, M.D., and described in the October issue of the journal Neurosurgery.
To conduct their experiments, Garzon-Muvdi and his colleagues took blood from mouse leg arteries and injected it behind their necks to mimic what happens in a subarachnoid hemorrhage. Then they gave the mice a compound called (S)-4-carboxyphenylglycine (S-4-CPG), a placebo or nothing at all. The mice given S-4-CPG developed less vasospasm, looked better and were more active than those in the other two groups.
The scientists also found concentrations of the drug in the brains of the mice, showing that it was able to cross the often impermeable blood-brain barrier. The researchers chose the compound because it is similar to drugs that have been used in stroke research in rodents. It is not approved for any use in humans.
Garzon-Muvdi explains that when blood vessels break anywhere but the brain, the body’s immune cells easily clear the blood cells and their remnants from the area. This is what happens with a bruise, when immune cells rush to the area, and a chemical cascade scavenges and disperses the remnants of excess blood components.
When a blood vessel bursts in the space around the brain, however, the blood is trapped. A subsequent inflammatory response brings key immune system cells into the space, where they secrete the neurotransmitter glutamate outside of the blood vessels where it shouldn’t be, promoting dangerous vasospasm in those blood vessels. This can lead to ischemic stroke, the most common type of stroke, caused by a blockage of a blood vessel in the brain. Death or serious disability may result.
The Johns Hopkins researchers say S-4-CPG keeps glutamate “in check,” prevents or reduces vasospasm and allows oxygen-filled blood to continue flowing into the brain.
According to the National Institutes of Health, subarachnoid hemorrhage caused by a cerebral aneurysm that breaks open occurs in about 40 to 50 out of 100,000 people over age 30. Patients may die immediately, but those who survive are still at elevated risk for developing an ischemic stroke in the days afterward. These patients are often watched very carefully in the intensive care unit for one to two weeks to search for early signs of vasospasm so that doctors can take steps to prevent or limit damage from a stroke.
In the ICU, doctors can order regular angiograms or ultrasounds to measure blood flow in vessels. If need be, they can increase blood pressure to send blood through vessels faster in the hopes of counteracting the constriction.
A drug to prevent stroke after a serious subarachnoid hemorrhage that follows the rupture of an aneurysm would improve quality of life for patients, Garzon-Muvdi says, and could potentially save millions of dollars in health care costs if patients don’t have to endure extensive hospital stays to monitor for a delayed stroke.
Researchers at The University of Texas at Dallas have taken a step toward developing a new treatment to aid the recovery of limb function after strokes.
In a study published online in the journal Neurobiology of Disease, researchers report the full recovery of forelimb strength in animals receiving vagus nerve stimulation.
“Stroke is a leading cause of disability worldwide,” said Dr. Navid Khodaparast, a postdoctoral researcher in the School of Behavioral and Brain Sciences and lead author of the study. “Every 40 seconds, someone in the U.S. has a stroke. Our results mark a major step in the development of a possible treatment.”
Vagus nerve stimulation (VNS) is an FDA-approved method for treating various illnesses, such as depression and epilepsy. It involves sending a mild electric pulse through the vagus nerve, which relays information about the state of the body to the brain.
Khodaparast and his colleagues used vagus nerve stimulation precisely timed to coincide with rehabilitative movements in rats. Each of the animals had previously experienced a stroke that impaired their ability to pull a handle.
Stimulation of the vagus nerve causes the release of chemicals in the brain known to enhance learning and memory called neurotransmitters, specifically acetylcholine and norepinephrine. Pairing this stimulation with rehabilitative training allowed Khodaparast and colleagues to improve recovery.
Many rehabilitative interventions try to enhance neuroplasticity (the brain’s ability to change) in conjunction with physical rehabilitation to drive the recovery of lost functions, according to Khodaparast. Unfortunately, up to 70 percent of stroke patients still display long-term impairment in arm function after traditional rehabilitation.
“For years, the majority of stroke patients have received treatment with various drugs and/or physical rehabilitation,” Khodaparast said. “Medications can have widespread effects in the brain and the effects can last for long periods of time. In some cases the side effects outweigh the benefits. Through the use of VNS, we are able to use the brain’s natural way of changing its neural circuitry and provide specific and long lasting effects.”
Khodaparast acknowledged the study has some limitations. For example, the animals were young and lacked some of the other illnesses that accompany an aged human population, such as diabetes or hypertension. But Khodaparast and his colleagues said they are optimistic about vagus nerve stimulation as a future tool. They will continue testing in chronically impaired animals with the hopes of translating the technique for stroke patients. Working with MicroTransponder Inc., a partner company in the current study, researchers at the University of Glasgow in Scotland have begun a small-scale trial in humans.
“There is strong evidence that VNS can be used safely in stroke patients because of its extensive use in the treatment of other neurological conditions,” said Dr. Michael Kilgard, professor in neuroscience at UT Dallas and senior author of the study.
Kilgard is also conducting clinical trials using vagus nerve stimulation to treat tinnitus, the medical condition of unexplained ringing in the ears. Kilgard’s lab first demonstrated the ability of vagus nerve stimulation to enhance brain adaptability in a 2011 Nature paper.
Your eyes may be a window to your stroke risk.
In a study reported in the American Heart Association journal Hypertension, researchers said retinal imaging may someday help assess if you’re more likely to develop a stroke — the nation’s No. 4 killer and a leading cause of disability.
“The retina provides information on the status of blood vessels in the brain,” said Mohammad Kamran Ikram, M.D., Ph.D., lead author of the study and assistant professor in the Singapore Eye Research Institute, the Department of Ophthalmology and Memory Aging & Cognition Centre, at the National University of Singapore. “Retinal imaging is a non-invasive and cheap way of examining the blood vessels of the retina.”
Worldwide, high blood pressure is the single most important risk factor for stroke. However, it’s still not possible to predict which high blood pressure patients are most likely to develop a stroke.
Researchers tracked stroke occurrence for an average 13 years in 2,907 patients with high blood pressure who had not previously experienced a stroke. At baseline, each had photographs taken of the retina, the light-sensitive layer of cells at the back of the eyeball. Damage to the retinal blood vessels attributed to hypertension — called hypertensive retinopathy — evident on the photographs was scored as none, mild or moderate/severe.
During the follow-up, 146 participants experienced a stroke caused by a blood clot and 15 by bleeding in the brain.
Researchers adjusted for several stroke risk factors such as age, sex, race, cholesterol levels, blood sugar, body mass index, smoking and blood pressure readings. They found the risk of stroke was 35 percent higher in those with mild hypertensive retinopathy and 137 percent higher in those with moderate or severe hypertensive retinopathy.
Even in patients on medication and achieving good blood pressure control, the risk of a blood clot was 96 percent higher in those with mild hypertensive retinopathy and 198 percent higher in those with moderate or severe hypertensive retinopathy.
“It is too early to recommend changes in clinical practice,” Ikram said. “Other studies need to confirm our findings and examine whether retinal imaging can be useful in providing additional information about stroke risk in people with high blood pressure.”
About nine months after suffering a stroke, the patient noticed that words written in a certain shade of blue evoked a strong feeling of disgust. Yellow was only slightly better. Raspberries, which he never used to eat very often, now tasted like blue – and blue tasted like raspberries.
High-pitched brass instruments—specifically the brass theme from James Bond movies—elicited feelings of ecstasy and light blue flashes in his peripheral vision and caused large parts of his brain to light up on an MRI. Music played by a euphonium, a tenor-pitched brass instrument, shut down those sensations.
The patient said he was initially frightened by the mixed messages his brain was sending him and the conflicting senses he was experiencing. He was so worried that something was seriously wrong with him that he raised it with a nurse only as he was leaving an appointment at St. Michael’s Hospital in downtown Toronto.
Physicians and researchers immediately recognized he had synesthesia, a neurological condition in which people experience more than one sense at the same time. They may “see” words or numbers as colours, hear sounds in response to smells or feel something in response to sight.
Most synesthetes are born with the condition, and include some of the world’s most famous authors and artists, including author Vladimir Nabakov, composer Franz Liszt, painter Vasily Kandinsky and singer-songwriter Billy Joel.
The Toronto patient is only the second known person to have acquired synesthesia as a result of a brain injury, in this case a stroke. His case was described in the August issue of the journal Neurology by Dr. Tom Schweizer, a neuroscientist and director of the Neuroscience Research Program at St. Michael’s Li Ka Shing Knowledge Institute.
Dr. Schweizer examined the patient’s brain activity in a functional MRI and compared it to six men of similar age (45) and education (18 years) as each listened to the James Bond Theme and a euphonium solo.
When the James Bond Theme was played, large areas of the patient’s brain lit up including the thalamus (the brain’s information switchboard), the hippocampus (which deals with memory and spatial navigation) and the auditory cortex (which processes sound).
"The areas of the brain that lit up when he heard the James Bond Theme are completely different from the areas we would expect to see light up when people listen to music," Dr. Schweizer said. "Huge areas on both sides of the brain were activated that were not activated when he listened to other music or other auditory stimuli and were not activated in the control group."
The patient and members of the control group also viewed 10-second blocks of words presented in black (which elicits no emotional response in the patient), yellow (mild disgust response) and blue (intense disgust response).
Reading blue letters produced extensive activity in the parts of the patient’s brain responsible for sensory information and processing emotional stimuli and similar but less intense responses for yellow letters. Control groups showed no heightened brain activity in response to the different coloured letters.
Dr. Schweizer said the fact that the patient had very targeted and specific responses to certain stimuli – and that these responses were not experienced by the control group – suggests that his synesthesia was caused as his brain tried to repair itself after his stroke and got cross-wired.
The patient’s stroke occurred in the thalamus, the brain’s central relay station. That’s the same part of the brain affected by the only other reported case of acquired synesthesia.
Researchers studying a type of cell found in the trillions in our brain have made an important discovery as to how it responds to brain injury and disease such as stroke. A University of Bristol team has identified proteins which trigger the processes that underlie how astrocyte cells respond to neurological trauma.
The star-shaped astrocytes, which outnumber neurons in humans, are a type of glial cell that comprise one of two main categories of cell found in the brain along with neurons. The cells, which have branched extensions that reach synapses (the connections between neurons) blood vessels, and neighbouring astrocytes, play a pivotal role in almost all aspects of brain function by supplying physical and nutritional support for neurons. They also contribute to the communication between neurons and the response to injury.
However, the cells are also known to trigger both beneficial and detrimental effects in response to neurological trauma. When the brain is subjected to injury or disease, the cells react in a number of ways, including a change in shape. In severe cases, the altered cells form a scar, which is thought to have beneficial, as well as detrimental effects by allowing prompt repair of the blood-brain barrier, and limiting cell death, but also impairing the regeneration of nerve fibres and the effective incorporation of neuronal grafts - where additional neuronal cells are added to the injured site.
The cells change shape via the regulation of a structural component of the cell called the actin cytoskeleton, which is made up of filaments that shrink and grow to physically manoeuvre parts of the cell. In the lab, the team cultured astrocytes in a dish and were able to make them change shape by chemically or genetically manipulating proteins that control actin, and also by mimicking the environment that the cells would be exposed to during a stroke.
By doing so the team found that very dramatic changes in cell shape were caused by controlling the actin cytoskeleton in the in vitro stroke model. The team also identified additional protein molecules that control this process, suggesting that a complex mechanism is involved.
Dr Jonathan Hanley from the University’s School of Biochemistry said: “Our findings are crucial to our understanding of how the brain responds to many disorders that affect millions of people every year. Until now, the details of the actin-based mechanisms that control astrocyte morphology were unknown, so we anticipate that our work will lead to future discoveries about this important process.”