Category: Neurology

Categories : NeurologyTags :

People with ‘Young Brains’ Outlive ‘Old-brained’ Peers, Research Finds

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Image created with Gencraft AI

A blood-test analysis developed at Stanford Medicine can determine the “biological ages” of 11 separate organ systems in individuals’ bodies and predict the health consequences.

Beside our chronological age, research has shown that we also have what’s called a “biological age,” a cryptic but more accurate measure of our physiological condition and likelihood of developing aging-associated disorders from heart trouble to Alzheimer’s disease.

How old someone’s internal organs are is a challenge to determine compared to looking at wrinkles and greying hair. Internal organs are ageing at different speeds, too, according to a new study by Stanford Medicine investigators.

“We’ve developed a blood-based indicator of the age of your organs,” said Tony Wyss-Coray, PhD, professor of neurology and neurological sciences and director of the Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute. “With this indicator, we can assess the age of an organ today and predict the odds of your getting a disease associated with that organ 10 years later.”

They can even predict who is most likely to die from medical conditions associated with one or more of the 11 separate organ systems the researchers looked at: brain, muscle, heart, lung, arteries, liver, kidneys, pancreas, immune system, intestine and fat.

The brain is the gatekeeper of longevity. If you’ve got an old brain, you have an increased likelihood of mortality. If you’ve got a young brain, you’re probably going to live longer.”

The biological age of one organ, the brain, plays an outsized role in determining how long you have left to live, Wyss-Coray said.

“The brain is the gatekeeper of longevity,” he said. “If you’ve got an old brain, you have an increased likelihood of mortality. If you’ve got a young brain, you’re probably going to live longer.”

Wyss-Coray is the senior author of the study, published online July 9 in Nature Medicine. The lead author is Hamilton Oh, PhD, a former graduate student in Wyss-Coray’s group.

Eleven organ systems, 3000 proteins, 45 000 people

The scientists used 44 498 randomly selected participants, ages 40 to 70, who were drawn from the UK Biobank. This ongoing effort has collected multiple blood samples and updated medical reports from some 600 000 individuals over several years. These participants were monitored for up to 17 years for changes in their health status.

Wyss-Coray’s team made use of an advanced commercially available laboratory technology that counted the amounts of nearly 3000 proteins in each participant’s blood. Some 15% of these proteins can be traced to single-organ origins, and many of the others to multiple-organ generation.

The researchers fed everybody’s blood-borne protein levels into a computer and determined the average levels of each of those organ-specific proteins in the blood of those people’s bodies, adjusted for age. From this, the scientists generated an algorithm that found how much the composite protein “signature” for each organ being assessed differed from the overall average for people of that age.

Based on the differences between individuals’ and age-adjusted average organ-assigned protein levels, the algorithm assigned a biological age to each of the 11 distinct organs or organ systems assessed for each subject. And it measured how far each organ’s multiprotein signature in any given individual deviated in either direction from the average for people of the same chronological age. These protein signatures served as proxies for individual organs’ relative biological condition. A greater than 1.5 standard deviation from the average put a person’s organ in the “extremely aged” or “extremely youthful” category.

One-third of the individuals in the study had at least one organ with a 1.5-or-greater standard deviation from the average, with the investigators designating any such organ as “extremely aged” or “extremely youthful.” One in four participants had multiple extremely aged or youthful organs.

For the brain, “extremely aged” translated to being among the 6% to 7% of study participants’ brains whose protein signatures fell at one end of the biological-age distribution. “Extremely youthful” brains fell into the 6% to 7% at the opposite end.

Health outcomes foretold

The algorithm also predicted people’s future health, organ by organ, based on their current organs’ biological age. Wyss-Coray and his colleagues checked for associations between extremely aged organs and any of 15 different disorders including Alzheimer’s and Parkinson’s diseases, chronic liver or kidney disease, Type 2 diabetes, two different heart conditions and two different lung diseases, rheumatoid arthritis and osteoarthritis, and more.

Risks for several of those diseases were affected by numerous different organs’ biological age. But the strongest associations were between an individual’s biologically aged organ and the chance that this individual would develop a disease associated with that organ. For example, having an extremely aged heart predicted higher risk of atrial fibrillation or heart failure, having aged lungs predicted heightened chronic obstructive pulmonary disease (COPD) risk, and having an old brain predicted higher risk for Alzheimer’s disease.

The association between having an extremely aged brain and developing Alzheimer’s disease was particularly powerful: 3.1 times that of a person with a normally aging brain. Meanwhile, having an extremely youthful brain was especially protective against Alzheimer’s – barely one-fourth that of a person with a normally aged brain.

In addition, Wyss-Coray said, brain age was the best single predictor of overall mortality. Having an extremely aged brain increased subjects’ risk of dying by 182% over a roughly 15-year period, while individuals with extremely youthful brains had an overall 40% reduction in their risk of dying over the same duration.

Predicting the disease, then preventing it

“This approach could lead to human experiments testing new longevity interventions for their effects on the biological ages of individual organs in individual people,” Wyss-Coray said.

Medical researchers may, for example, be able to use extreme brain age as a proxy for impending Alzheimer’s disease and intervene before the onset of outward symptoms, when there’s still time to arrest it, he said.

Careful collection of lifestyle, diet and prescribed- or supplemental-substance intake in clinical trials, combined with organ-age assessments, could throw light on the medical value of those factors’ contributions to the aging of various organs, as well as on whether existing, approved drugs can restore organ youth before people develop a disease for which an organ’s advanced biological age puts them at high risk, Wyss-Coray added.

If commercialised, the test could be available in the next two to three years, Wyss-Coray said. “The cost will come down as we focus on fewer key organs, such as the brain, heart and immune system, to get more resolution and stronger links to specific diseases.”

Source: Stanford University

Categories : Neurology Pain ManagementTags :

From Injury to Agony: The Brain Pathway that Turns Pain into Suffering

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Salk scientists uncover a key neural circuit in mice that gives pain its emotional punch, opening new doors for treating fibromyalgia, migraine, and PTSD


CGRP-expressing neurons (green) in the parvocellular subparafascicular nucleus (SPFp) of the thalamus.
Credit: Salk Institute

More than just a physical sensation, pain also carries emotional weight. That distress, anguish, and anxiety can turn a fleeting injury into long-term suffering.

Salk Institute researchers have now identified a brain circuit that gives physical pain its emotional tone, revealing a new potential target for treating chronic and affective pain conditions such as fibromyalgia, migraine, and post-traumatic stress disorder (PTSD).

Published in PNAS, the study identifies a group of neurons in a central brain area called the thalamus that appears to mediate the emotional or affective side of pain in mice. This new pathway challenges the textbook understanding of how pain is processed in the brain and body.

“For decades, the prevailing view was that the brain processes sensory and emotional aspects of pain through separate pathways,” says senior author Sung Han, associate professor and holder of the Pioneer Fund Developmental Chair at Salk. “But there’s been debate about whether the sensory pain pathway might also contribute to the emotional side of pain. Our study provides strong evidence that a branch of the sensory pain pathway directly mediates the affective experience of pain.”

The physical sensation of pain allows immediate detection, assessment of its intensity, and identification of its source. The affective part of pain is what makes it so unpleasant – the emotional discomfort motivates avoidance.

This is a critical distinction. Most people start to perceive pain at the same stimulus intensities, meaning the sensory side of pain is processed similarly. But the ability to tolerate pain varies greatly. The degree of suffering or feeling threatened by pain is determined by affective processing, and if that becomes too sensitive or lasts too long, it can result in a pain disorder. This makes it important to understand which parts of the brain control these different dimensions of pain.

Sensory pain was thought to be mediated by the spinothalamic tract, a pathway that sends pain signals from the spinal cord to the thalamus, which then relays them to sensory processing areas across the brain.

Affective pain was generally thought to be mediated by a second pathway called the spinoparabrachial tract, which sends pain information from the spinal cord into the brainstem.

However, previous studies using older research methods have suggested the circuitry of pain may be more complex. This long-standing debate inspired Han and his team to revisit the question with modern research tools.

Using advanced techniques to manipulate the activity of specific brain cells, the researchers discovered a new spinothalamic pathway in mice. In this circuit, pain signals are sent from the spinal cord into a different part of the thalamus, which has connections to the amygdala, the brain’s emotional processing center. This particular group of neurons in the thalamus can be identified by their expression of CGRP (calcitonin gene-related peptide), a neuropeptide originally discovered in Professor Ronald Evans’ lab at Salk.

When the researchers “turned off” (genetically silenced) these CGRP neurons, the mice still reacted to mild pain stimuli, such as heat or pressure, indicating their sensory processing was intact. However, they didn’t seem to associate lasting negative feelings with these situations, failing to show any learned fear or avoidance behaviors in future trials. On the other hand, when these same neurons were “turned on” (optogenetically activated), the mice showed clear signs of distress and learned to avoid that area, even when no pain stimuli had been used.

“Pain processing is not just about nerves detecting pain; it’s about the brain deciding how much that pain matters,” says first author Sukjae Kang, a senior research associate in Han’s lab. “Understanding the biology behind these two distinct processes will help us find treatments for the kinds of pain that don’t respond to traditional drugs.”

Many chronic pain conditions—such as fibromyalgia and migraine—involve long, intense, unpleasant experiences of pain, often without a clear physical source or injury. Some patients also report extreme sensitivity to ordinary stimuli like light, sound, or touch, which others would not perceive as painful.

Han says overactivation of the CGRP spinothalamic pathway may contribute to these conditions by making the brain misinterpret or overreact to sensory inputs. In fact, transcriptomic analysis of the CGRP neurons showed that they express many of the genes associated with migraine and other pain disorders.

Notably, several CGRP blockers are already being used to treat migraines. This study may help explain why these medications work and could inspire new nonaddictive treatments for affective pain disorders.

Han also sees potential relevance for psychiatric conditions that involve heightened threat perception, such as PTSD. Growing evidence from his lab suggests that the CGRP affective pain pathway acts as part of the brain’s broader alarm system, detecting and responding to not only pain but a wide range of unpleasant sensations. Quieting this pathway with CGRP blockers could offer a new approach to easing fear, avoidance, and hypervigilance in trauma-related disorders.

Importantly, the relationship between the CGRP pathway and the psychological pain associated with social experiences like grief, loneliness, and heartbreak remains unclear and requires further study.

“Our discovery of the CGRP affective pain pathway gives us a molecular and circuit-level explanation for the difference between detecting physical pain and suffering from it,” says Han. “We’re excited to continue exploring this pathway and enabling future therapies that can reduce this suffering.”

Source: Salk Institute

Categories : NeurologyTags :

New Research Confirms that Neurons Form in the Adult Brain

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A healthy neuron. Credit: NIH

A study in the journal Science presents compelling new evidence that neurons in the brain’s memory centre, the hippocampus, continue to form well into late adulthood. The research from Karolinska Institutet provides answers to a fundamental and long-debated question about the human brain’s adaptability.

The hippocampus is a brain region that is essential for learning and memory and involved in emotion regulation. Back in 2013, Jonas Frisén’s research group at Karolinska Institutet showed in a high-profile study that new neurons can form in the hippocampus of adult humans. The researchers then measured carbon-14 levels in DNA from brain tissue, which made it possible to determine when the cells were formed.

Identifying cells of origin

However, the extent and significance of this formation of new neurons (neurogenesis) are still debated. There has been no clear evidence that the cells that precede new neurons, known as neural progenitor cells, actually exist and divide in adult humans.

“We have now been able to identify these cells of origin, which confirms that there is an ongoing formation of neurons in the hippocampus of the adult brain,” says lead researcher Jonas Frisén, professor of stem cell research at the Department of Cell and Molecular Biology.

In the new study, the researchers combined several advanced methods to examine brain tissue from people aged 0 to 78 years from several international biobanks. They used a method called single-nucleus RNA sequencing, which analyses gene activity in individual cell nuclei, and flow cytometry to study cell properties. 

By combining this with machine learning, they were able to identify different stages of neuronal development, from stem cells to immature neurons, many of which were in the division phase.

To localise these cells, the researchers used two techniques that show where in the tissue different genes are active: RNAscope and Xenium. These methods confirmed that the newly formed cells were located in a specific area of the hippocampus called the dentate gyrus. This area is important for memory formation, learning and cognitive flexibility.

Hope for new treatments

The results show that the progenitors of adult neurons are similar to those of mice, pigs and monkeys, but that there are some differences in which genes are active. There were also large variations between individuals – some adult humans had many neural progenitor cells, others hardly any at all.

“This gives us an important piece of the puzzle in understanding how the human brain works and changes during life,” explains Jonas Frisén. “Our research may also have implications for the development of regenerative treatments that stimulate neurogenesis in neurodegenerative and psychiatric disorders.” 

Source: Karolinska Institutet

Categories : Diseases, Syndromes and Conditions NeurologyTags :

Toxoplasma Gondii’s Disruption of the Brain Gives Clues to New Treatments

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Source: Wikimedia CC0

A team of scientists at the University of California, Riverside, explains in a paper published in PLoS Pathogens how the microscopic parasite Toxoplasma gondii can significantly disrupt brain function, even when it infects only a small number of neurons. The team found the parasite interferes with essential communication between brain cells — research that can offer new ways to detect and treat chronic brain infections.

Toxoplasma gondii can infect nearly any warm-blooded animal and prefers to live inside brain cells, forming cysts in neurons that can persist for life. The researchers report that they found infected neurons release fewer extracellular vesicles (EVs) — tiny, membrane-bound packets used by cells to exchange information. 

“We found this disruption in EV signalling can interfere with how neurons and glial cells, especially astrocytes, maintain a healthy brain environment,” said Emma H. Wilson, a professor of biomedical sciences in the UC Riverside School of Medicine who led the research team. “Even a handful of infected neurons can shift the brain’s neurochemical balance. This suggests that communication between neurons and supporting glial cells is not only critical, but also vulnerable to hijacking by parasites.”

Approximately 10–30% of people in the United States are infected with Toxoplasma gondii, often without knowing it. The parasite is typically contracted through undercooked meat or exposure to cat feces. Although the immune system typically keeps the infection in check, the parasite can lie dormant in the brain for decades. In individuals with weakened immunity, it can reactivate and cause serious illness.

Current diagnostic tools can only detect whether someone has been exposed to Toxoplasma gondii by identifying antibodies. The tools cannot confirm whether the parasite is still present in the brain or how it may be affecting brain function.

“Our research opens the door to using EVs as biomarkers, which can be isolated from blood,” Wilson said. 

The study was conducted using mouse models and human cells in a laboratory setting.

Wilson explained that in healthy mouse brains astrocytes regulate neurotransmitters like glutamate, ensuring that neurons do not become overexcited. But when neurons infected with Toxoplasma gondii stop sending the right EV signals, this regulation breaks down. The result is elevated glutamate levels, which can lead to seizures, neural damage, or altered brain connectivity.

“The parasite may play a larger role in neurological and behavioural conditions than we previously thought,” she said.

Wilson’s research team is now working to analyse samples from human blood banks to look for EVs linked to Toxoplasma gondii brain infection. The team also hopes to better understand how glial cells detect and respond to parasite proteins — insights that could one day lead to new therapies or even vaccines.

“Our brains have built-in defences that may recognise and respond to neurons infected by Toxoplasma gondii,” Wilson said. “If we can learn how to support or enhance that process, we may be able to better protect people, especially the most vulnerable.”

Despite its potential impact, Toxoplasma gondii is often misunderstood, Wilson added. 

“There’s no need to avoid someone who is infected; most people live their entire lives without symptoms,” she said. “Pregnant individuals should be cautious as the parasite can cause serious birth defects if contracted for the first time during pregnancy. The most effective prevention is proper food handling and hygiene. Cook meat thoroughly, wash vegetables, and always wash your hands after handling cat litter, especially from young cats, which are more likely to shed the parasite.”

Source: University of California, Riverside

Categories : Metabolic Disorders NeurologyTags :

Diabetes Drug May Serve as Alternative Treatment Option for Hydrocephalus

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Photo by Anna Shvets

A drug commonly used to treat type 2 diabetes may reduce excess fluid in the brains of patients with hydrocephalus, which could help treat the disease less invasively than current treatments, according to a Northwestern Medicine study published in the Journal of Clinical Investigation.

Normal pressure hydrocephalus occurs when excess cerebrospinal fluid builds up inside the skull and puts pressure on the brain. The cause of the condition is elusive and affects up to three percent of individuals over the age of 65, with symptoms including cognitive decline, difficulty walking and bladder problems.  

Patients are typically treated with permanent ventriculoperitoneal shunts, which are surgically implanted in the front or back of the skull and are connected to a valve that diverts excess cerebrospinal fluid away from the brain and into the abdomen where it is absorbed. The procedure has been shown to dramatically improve mobility, bladder control and cognitive functioning in patients with hydrocephalus, according to senior study author Stephen Magill, MD, PhD.

“It’s a great procedure because it’s one of the few things you can do that actually reverses these symptoms,” said Magill, who is assistant professor of Neurological Surgery.

There is, however, no pharmacological treatment currently approved to treat hydrocephalus. Additionally, nearly 20% of patients with normal pressure hydrocephalus also have type 2 diabetes and take sodium/glucose cotransporter 2 (SGLT2) inhibitors to manage their blood sugar, cardiovascular and kidney function, and weight loss.

Magill recently observed a reduction in the brain ventricle size in a patient with hydrocephalus who had a ventriculoperitoneal shunt surgically implanted and then began taking SGLT2 inhibitors to treat their type 2 diabetes. This phenomenon prompted Magill to further investigate the impact of SGLT2 inhibitors on ventricular size in patients with hydrocephalus.

“The medication inhibits a receptor found in the kidneys, which is where it works for diabetes. However, that receptor is also expressed in the choroid plexus, which is the structure in the brain that secretes the spinal fluid. Although this was known from animal studies, the clinical aspects of this biology have not been fully appreciated,” Magill said.

In the current study, three patients with hydrocephalus underwent CT scans both before and after surgery for ventriculoperitoneal shunts. After surgery, each patient began taking SGLT2 inhibitors for a medical indication and then underwent additional CT scans.

From analyzing these scans, Magill’s team discovered that all three patients showed a reduction in ventricle size as well as structural changes in their brains after starting SGLT2 therapy. One patient demonstrated dramatic ventricle size reduction due to ventricular collapse and required a shunt valve adjustment to reduce cerebrospinal fluid drainage.

“It’s a really interesting clinical observation because it raises the possibility that these medications could be used to treat normal pressure hydrocephalus in the future, which would normally require surgery,” Magill said.

Magill said the findings have sparked a new line of research in studying how SGLT2 inhibitors could help prevent hydrocephalus, adding that his team is now studying SGLT2 knockout mouse models to better understand the drug’s impact on ventricular size.

Their findings could ultimately inform new therapeutic strategies for treating normal pressure hydrocephalus as well as post-traumatic hydrocephalus, or the buildup of cerebrospinal fluid after traumatic brain injury, according to Magill.

“This sparks a new line of research on how normal pressured hydrocephalus develops, what causes it, how this protein works in creating and secreting spinal fluid, and has direct translational implications,” Magill said. “There’s a whole new avenue of potentially treating this disease that might save a patient from having surgery, and there’s always risks with surgery. It will also evolve our understanding of how these drugs work.”

Source: Northwestern Medicine

Categories : Cancer NeurologyTags :

New Strategy for the Treatment of Severe Childhood Cancer

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Credit: National Cancer Institute

Researchers at Karolinska Institutet and Lund University have identified a new treatment strategy for neuroblastoma, an aggressive form of childhood cancer. By combining two antioxidant enzyme inhibitors, they have converted cancer cells in mice into healthy nerve cells. The study is published in the journal Proceedings of the National Academy of Sciences (PNAS).

Neuroblastoma is a type of childhood cancer that affects the nervous system and is the leading cause of cancer-related death in young children. Some patients have a good prognosis, but those with metastatic tumours often cannot be cured despite modern combinations of surgery, radiation, chemotherapy and immunotherapy.

“The children who survive often have lifelong cognitive difficulties due to the harsh treatment, so there is a great need for new forms of therapies for children with neuroblastoma,” says Marie Arsenian Henriksson, professor at the Department of Microbiology, Tumour and Cell Biology at Karolinska Institutet.

Transform cancer cells

Differentiation therapy is a treatment method used in neuroblastoma that aims to transform cancer cells into more mature and healthy cells. The problem with the current retinoic acid differentiation therapy is that many patients do not respond to treatment, and about half develop resistance.

In collaboration with researchers at Lund University, Marie Arsenian Henriksson’s research team has shown that inhibition of two specific enzymes, PRDX6 and GSTP1, could be an alternative to retinoic acid treatment.

Mature into healthy neurons

Neuroblastoma is characterised by high oxidative stress due to the active metabolism in the cancer cells. Tumours are therefore dependent on antioxidant enzymes such as PRDX6 and GSTP1 to manage the stress and avoid cell death. High levels of these enzymes are associated with a poorer prognosis.

“When we inhibit these enzymes in cell cultures as well as in mouse models, some of the tumour cells die while others mature into active, healthy neurons, impairing tumour growth,” says Judit Liaño-Pons, researcher at the Department of Microbiology, Tumour and Cell Biology.

Needs to be tested in children

In the next step, the treatment will need to be tested in a clinical trial to investigate its safety and efficacy in children. One of the inhibitors has received orphan drug designation from the US Food and Drug Administration for the treatment of a different diagnosis in adults, making it a particularly promising drug candidate, according to the scientists.

Source: Karolinska Institutet

Categories : Cardiovascular Disease NeurologyTags :

Study Finds that Cognitive Impairment is Common After Cardiogenic Shock

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Pexels Photo by Freestocksorg

Many survivors of cardiogenic shock showed evidence of new cognitive impairment after leaving the hospital, according to a study led by UT Southwestern Medical Center researchers. The findings, published in the Journal of the American College of Cardiology, highlight a need to screen survivors and provide referrals to neuropsychology experts, the authors said.

“Our study demonstrated that nearly two-thirds of cardiogenic shock survivors experienced cognitive impairment within three months of hospital discharge, underscoring a critical but overlooked aspect of recovery,” said senior investigator James de Lemos, MD, Professor of Internal Medicine and Chief of the Division of Cardiology at UT Southwestern. “The findings are important for developing interventions that focus not only on improving survival but also on preventing or mitigating the functional consequences of cardiogenic shock, including cognitive decline.”

Cardiogenic shock results from heart failure, heart attack, or complications following cardiac surgery, and is characterised by a sudden drop in heart pumping ability. It results in acute hypoperfusion and hypoxia of the organs and has historically resulted in high mortality.

With advances in treatment during the past two decades, up to 70% of patients suffering from cardiogenic shock can now survive. But there is limited understanding of survivors’ recovery and quality of life after they leave the hospital.

“Our study is the first to systematically examine the cognitive outcomes of cardiogenic shock survivors, evaluating how cognition impacts patients’ ability to return to daily activities,” said Eric Hall, M.D., a clinical fellow in the Division of Cardiology who was the study leader and first author. “We found that cardiogenic shock is associated with cognitive impairment, which is an under-recognized consequence strongly linked to patients’ overall quality of life.”

UTSW researchers conducted the study by enrolling 141 patients who had survived cardiogenic shock before being discharged. To establish a baseline, family members completed a questionnaire, the AD8 survey, about the patients’ cognitive function before hospitalisation.

Before discharge, each patient completed the Montreal Cognitive Assessment-Blind (bMoCA) to screen for signs of cognitive impairment. Three months after discharge, patients repeated the assessments, allowing researchers to track changes in thinking ability and daily functioning over time.

Among patients with no sign of cognitive impairment before admission, 65% were found to have new impairment at discharge, and 53% continued to show impairment at their three-month follow-up. UTSW researchers emphasized that these findings should inform the development of comprehensive survivorship programs including screening protocols to identify impairments patients face and rehabilitation programs to help them recover from those challenges.

“We hope to use this study as a foundation to develop targeted rehabilitation strategies that connect patients with neuropsychology experts and improve long-term recovery in cardiogenic shock survivors,” Dr de Lemos said.

Source: UT Southwestern Medical Center

Categories : Injury & Trauma NeurologyTags :

Healing Spinal Cord Injuries with the Help of Electricity

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Heals spinal cord injuries with the help of electricity. Researchers have developed an ultra-thin implant that can be placed directly on the spinal cord. The implant delivers a carefully controlled electrical current across the injured area. In a recent study, researchers were able to observe how the electrical field treatment led to improved recovery in rats with spinal cord injuries, and that the animals regained movement and sensation. Please note that the image shows a newer model of the implant used in the study. Photo and illustration: University of Auckland

Researchers at Chalmers University of Technology in Sweden and the University of Auckland in New Zealand have developed a groundbreaking bioelectric implant that restores movement in rats after injuries to the spinal cord.

This breakthrough, published in Nature Communications, offers new hope for an effective treatment for humans suffering from loss of sensation and function due to spinal cord injury.

Electricity stimulated nerve fibres to reconnect

Before birth, and to a lesser extent afterwards, naturally occurring electric fields play a vital role in early nervous system development, encouraging and guiding the growth of nerve fibres along the spinal cord. Scientists are now harnessing this same electrical guidance system in the lab.

“We developed an ultra-thin implant designed to sit directly on the spinal cord, precisely positioned over the injury site in rats,” says Bruce Harland, senior research fellow, University of Auckland, and one of the lead researchers of the study.

The device delivers a carefully controlled electrical current across the injury site.

“The aim is to stimulate healing so people can recover functions lost through spinal cord injury,” says Professor Darren Svirskis, University of Auckland, Maria Asplund, Professor of bioelectronics at Chalmers University of Technology.

She is, together with Darren Svirskis, University of Auckland,

In the study, researchers observed how electrical field treatment improved the recovery of locomotion and sensation in rats with spinal cord injury. The findings offer renewed hope for individuals experiencing loss of function and sensation due to spinal cord injuries.

“Long-term, the goal is to transform this technology into a medical device that could benefit people living with life-changing spinal-cord injuries,” says Maria Asplund.

The study presents the first use of a thin implant that delivers stimulation in direct contact with the spinal cord, marking a groundbreaking advancement in the precision of spinal cord stimulation.

“This study offers an exciting proof of concept showing that electric field treatment can support recovery after spinal cord injury,” says doctoral student Lukas Matter, Chalmers University of Technology, the other lead researcher alongside Harland.

Improved mobility after four weeks

Unlike humans, rats have a greater capacity for spontaneous recovery after spinal cord injury, which allowed researchers to compare natural healing with healing supported by electrical stimulation.

After four weeks, animals that received daily electric field treatment showed improved movement compared with those who did not. Throughout the 12-week study, they responded more quickly to gentle touch.

“This indicates that the treatment supported recovery of both movement and sensation,” Harland says.

“Just as importantly, our analysis confirmed that the treatment did not cause inflammation or other damage to the spinal cord, demonstrating that it was not only effective but also safe,” Svirskis says.

The next step is to explore how different doses, including the strength, frequency, and duration of the treatment, affect recovery, to discover the most effective recipe for spinal-cord repair.

Source: Chalmers University of Technology

Categories : Cardiovascular Disease NeurologyTags :

Early Anticoagulants Found to be Safe and Effective for AF Stroke Patients

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Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0

Patients with atrial fibrillation who have experienced a stroke would benefit greatly from earlier treatment than is currently recommended in UK guidelines, finds a new study led by UCL researchers.

The results of the CATALYST study, published in The Lancet, included data from four randomised trials with a total of 5441 patients across the UK, Switzerland, Sweden and the United States, who had all experienced a recent stroke (between 2017-2024) due to a blocked artery and atrial fibrillation (irregular heartbeat).

Patients had either started medication early (within four days of their stroke) or later (after five days or more).

The researchers found that starting direct oral anticoagulants (DOACs, which thin the blood to prevent it from clotting as quickly) within four days of having a stroke was safe, with no increase in bleeding into the brain. Additionally, early initiation of treatment significantly reduced the risk of another stroke due to bleeding or artery blockage by 30% compared to those who started treatment later.

People with atrial fibrillation who have had a stroke have an increased risk of having another stroke, but this risk can be reduced by taking anticoagulants.

Anticoagulants come with the rare but dangerous side effect of bleeding into the brain, and there is a lack of evidence about when is best to start taking them after a stroke. Current UK guidelines are varied, suggesting that those who have had a moderate or severe stroke should wait at least five days before starting blood-thinning treatments.

To tackle this question, the researchers investigated the impact of early compared to delayed anticoagulant treatment.

Chief Investigator, Professor David Werring (UCL Queen Square Institute of Neurology) said: “Our new study supports the early initiation of DOACs in clinical practice, offering better protection against further strokes for a wide range of patients.”

The researchers now hope that their findings will influence clinical guidelines and improve outcomes for stroke patients worldwide.

First author and main statistician, Dr Hakim-Moulay Dehbi (UCL Comprehensive Clinical Trials Unit), said: “By systematically combining the data from four clinical trials, we have identified with increased confidence, compared to the individual trials, that early DOAC initiation is effective.”

The CATALYST study builds on findings from the British Heart Foundation funded OPTIMAS study – where the UCL-led research team analysed 3621 patients with atrial fibrillation who had had a stroke between 2019 and 2024, across 100 UK hospitals.

Half of the participants began anticoagulant treatment within four days of their stroke (early), and the other half started treatment seven to 14 days after having a stroke (delayed). Patients were followed up after 90 days to assess several outcomes including whether they went on to have another stroke and whether they experienced bleeding in the brain.

Both the early and late groups experienced a similar number of recurrent strokes. Early treatment was found to be effective and did not increase the risk of a bleed into the brain.

Professor Nick Freemantle, Senior Investigator and Director of the UCL Comprehensive Clinical Trials Unit (CCTU) that co-ordinated the OPTIMAS trial, said: “The benefits of early initiation of blood-thinning treatment are clear: patients receive the definitive and effective long-term stroke prevention therapy promptly, rather than waiting. This approach ensures that crucial treatments are not delayed or missed, particularly for patients who are discharged from the hospital.”

Study limitations

The timing for starting blood-thinning medication was based on previous trial designs (such as OPTIMAS), which may not cover all possible scenarios. Additionally, not all participants were randomised to the same timing groups, so some data was excluded. Lastly, the study didn’t include many patients with very severe strokes, so the findings might not apply to those cases.

Source: University College London

Categories : Neurology Pain ManagementTags :

GLP-1 Therapy Reduces Brain Pressure and Migraine Frequency

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A diabetes medication that lowers brain fluid pressure has cut monthly migraine days by more than half, according to a new study presented at the European Academy of Neurology (EAN) Congress 2025

Photo by Kindel Media

A diabetes medication that lowers brain fluid pressure has cut monthly migraine days by more than half, according to a new study presented at the European Academy of Neurology (EAN) Congress 2025.1

Researchers at the Headache Centre of the University of Naples “Federico II” gave the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide to 26 adults with obesity and chronic migraine (defined as ≥ 15 headache days per month). Patients reported an average of 11 fewer headache days per month, while disability scores on the Migraine Disability Assessment Test dropped by 35 points, indicating a clinically meaningful improvement in work, study, and social functioning.

GLP-1 agonists have gained recent widespread attention, reshaping treatment approaches for several diseases, including diabetes and cardiovascular disease.2 In the treatment of type 2 diabetes, liraglutide helps lower blood sugar levels and reduce body weight by suppressing appetite and reducing energy intake.3,4,5

Importantly, while participants’ body-mass index declined slightly (from 34.01 to 33.65), this change was not statistically significant. An analysis of covariance confirmed that BMI reduction had no effect on headache frequency, strengthening the hypothesis that pressure modulation, not weight loss, drives the benefit.

“Most patients felt better within the first two weeks and reported quality of life improved significantly”, said lead researcher Dr Simone Braca. “The benefit lasted for the full three-month observation period, even though weight loss was modest and statistically non-significant.”

Patients were screened to exclude papilledema (optic disc swelling resulting from increased intracranial pressure) and sixth nerve palsy, ruling out idiopathic intracranial hypertension (IIH) as a confounding factor. Growing evidence closely links subtle increases in intracranial pressure to migraine attacks.6 GLP-1-receptor agonists such as liraglutide reduce cerebrospinal fluid secretion and have already proved effective in treating IIH.7 Therefore, building on these observations, Dr Braca and colleagues hypothesised that exploiting the same mechanism of action might ultimately dampen cortical and trigeminal sensitisation that underlie migraine.

“We think that, by modulating cerebrospinal fluid pressure and reducing intracranial venous sinuses compression, these drugs produce a decrease in the release of calcitonin gene-related peptide (CGRP), a key migraine-promoting peptide”, Dr Braca explained. “That would pose intracranial pressure control as a brand-new, pharmacologically targetable pathway.”

Mild gastrointestinal side effects (mainly nausea and constipation) occurred in 38% of participants but did not lead to treatment discontinuation.

Following this exploratory 12-week pilot study, a randomised, double-blind trial with direct or indirect intracranial pressure measurement is now being planned by the same research team in Naples, led by professor Roberto De Simone. “We also want to determine whether other GLP-1 drugs can deliver the same relief, possibly with even fewer gastrointestinal side effects”, Dr Braca noted.

If confirmed, GLP-1-receptor agonists could offer a new treatment option for the estimated one in seven people worldwide who live with migraine,8 particularly those who do not respond to current preventives. Given liraglutide’s established use in type 2 diabetes and obesity, it may represent a promising case of drug repurposing in neurology.

References

  1. Braca S., Russo C. et al. GLP-1R Agonists for the Treatment of Migraine: A Pilot Prospective Observational Study. Abstract A-25-13975. Presented at the 11th EAN Congress (Helsinki, Finland).
  2. Zheng, Z., Zong, Y., Ma, Y. et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Sig Transduct Target Ther 9, 234 (2024).
  3. Lin, C. H. et al. An evaluation of liraglutide including its efficacy and safety for the treatment of obesity. Expert Opin. Pharmacother. 21, 275–285 (2020).
  4. Moon, S. et al. Efficacy and safety of the new appetite suppressant, liraglutide: A meta-analysis of randomized controlled trials. Endocrinol. Metab. (Seoul.) 36, 647–660 (2021).
  5. Jacobsen, L. V., Flint, A., Olsen, A. K. & Ingwersen, S. H. Liraglutide in type 2 diabetes mellitus: clinical pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet. 55, 657–672 (2016).
  6. De Simone R, Sansone M, Russo C, Miele A, Stornaiuolo A, Braca S. The putative role of trigemino-vascular system in brain perfusion homeostasis and the significance of the migraine attack. Neurol Sci. 2022 Sep;43(9):5665-5672. doi: 10.1007/s10072-022-06200-x. Epub 2022 Jul 8. PMID: 35802218; PMCID: PMC9385793.
  7. Mitchell J.L., Lyons H.S., Walker J.K. et al. (2023). The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomised clinical trial. Brain. 146(5):1821-1830.
  8. Steiner T.J., Stovner L.J., Jensen, R. et al. (2020). Migraine remains second among the world’s causes of disability. The Journal of Headache and Pain. 21:137.

Source: EurekAlert!