Category: Neurology

Brains of People with Sickle Cell Disease Appear Older

Sickle cell disease. Credit: National Institutes of Health

Individuals with sickle cell disease are at a higher risk for stroke and resulting cognitive disability. But even in the absence of stroke, many such patients struggle with remembering, focusing, learning and problem solving, among other cognitive problems, with many facing challenges in school and in the workplace.

Now a multidisciplinary team of researchers and physicians at Washington University School of Medicine in St. Louis has published a study that helps explain how the illness might affect cognitive performance in sickle cell patients without a history of stroke. The study, appearing in JAMA Network Open, found such participants had brains that appeared older than expected for their age. Individuals experiencing economic deprivation, who struggle to meet basic needs, even in the absence of sickle cell disease, had more-aged appearing brains, the team also found.

“Our study explains how a chronic illness and low socioeconomic status can cause cognitive problems,” said Andria Ford, MD, a professor of neurology and chief of the section of stroke and cerebrovascular diseases at WashU Medicine and corresponding author on the study. “We found that such factors could impact brain development and/or aging, which ultimately affects the mental processes involved in thinking, remembering and problem solving, among others. Understanding the influence that sickle cell disease and economic deprivation have on brain structure may lead to treatments and preventive measures that potentially could preserve cognitive function.”

More than 200 young, Black adults with and without sickle cell disease, living in St. Louis and the surrounding region in eastern Missouri and southwestern Illinois, participated in brain MRI scans and cognitive tests. The researchers – including Yasheng Chen, DSc, an associate professor of neurology at WashU Medicine and senior author on the study – calculated each person’s brain age using a brain-age prediction tool that was developed using MRI brain scans from a diverse group of more than 14 000 healthy people of known ages. The estimated brain age was compared with the individual’s actual age.

The researchers found that participants with sickle cell disease had brains that appeared an average of 14 years older than their actual age. Sickle cell participants with older-looking brains also scored lower on cognitive tests.

The study also found that socioeconomic status correlates with brain age. On average, a seven-year gap was found between the brain age and the participants’ actual age in healthy individuals experiencing poverty. The more severe the economic deprivation, the older the brains of such study subjects appeared.

Healthy brains shrink as people age, while premature shrinking is characteristic of neurological illnesses such as Alzheimer’s disease. But a smaller brain that appears older can also result from stunted growth early in life. Sickle cell disease is congenital, chronically depriving the developing brain of oxygen and possibly affecting its growth from birth. Also, children exposed to long-term economic deprivation and poverty experience cognitive challenges that affect their academic performance, Ford explained.

As a part of the same study, the researchers are again performing cognitive tests and scanning the brains of the same healthy and sickle cell participants three years after their first scan to investigate if the older-looking brains aged prematurely, or if their development was stunted.

“A single brain scan helps measure the participants’ brain age only in that moment,” said Ford, who treats patients at Barnes-Jewish Hospital. “But multiple time points can help us understand if the brain is stable, initially capturing differences that were present since childhood, or prematurely aging and able to predict the trajectory of someone’s cognitive decline. Identifying who is at greatest risk for future cognitive disability with a single MRI scan can be a powerful tool for helping patients with neurological conditions.”

Source: WashU Medicine

New Flexible ‘Tentacle’ Electrodes can Precisely Record Brain Activity

A bundle of extremely fine electrode fibres in the brain (microscope image). (Image: Yasar TB et al. Nature Communications 2024, modified)

Researchers at ETH Zurich have developed ultra-flexible brain probes that accurately record brain activity without causing tissue damage. This technology, described in Nature Communications, opens up new avenues for the treatment of a range of neurological and neuropsychiatric disorders. 

Neurostimulators, also known as brain pacemakers, send electrical impulses to specific areas of the brain via special electrodes. It is estimated that some 200 000 people worldwide are now benefiting from this technology, including those who suffer from Parkinson’s disease or from pathological muscle spasms. According to Mehmet Fatih Yanik, Professor of Neurotechnology at ETH Zurich, further research will greatly expand the potential applications: instead of using them exclusively to stimulate the brain, the electrodes can also be used to precisely record brain activity and analyse it for anomalies associated with neurological or psychiatric disorders. In a second step, it would be conceivable in future to treat these anomalies and disorders using electrical impulses.

To this end, Yanik and his team have now developed a new type of electrode that enables more detailed and more precise recordings of brain activity over an extended period of time. These electrodes are made of bundles of extremely fine and flexible fibres of electrically conductive gold encapsulated in a polymer. Thanks to a process developed by the ETH Zurich researchers, these bundles can be inserted into the brain very slowly, which is why they do not cause any detectable damage to brain tissue.

This sets the new electrodes apart from rival technologies. Of these, perhaps the best known in the public sphere is the one from Neuralink, an Elon Musk company. In all such systems, including Neuralink’s, the electrodes are considerably wider. “The wider the probe, even if it is flexible, the greater the risk of damage to brain tissue,” Yanik explains. “Our electrodes are so fine that they can be threaded past the long processes that extend from the nerve cells in the brain. They are only around as thick as the nerve-cell processes themselves.”

The tentacle electrodes (right) shown alongside three current technologies using thicker electrodes or an electrode mesh. (Yasar TB et al. Nature Communications 2024, modified)

The research team tested the new electrodes on the brains of rats using four bundles, each made up of 64 fibres. In principle, as Yanik explains, up to several hundred electrode fibres could be used to investigate the activity of an even greater number of brain cells. In the study, the electrodes were connected to a small recording device attached to the head of each rat, thereby enabling them to move freely.

No influence on brain activity

In the experiments, the research team was able to confirm that the probes are biocompatible and that they do not influence brain function. Because the electrodes are very close to the nerve cells, the signal quality is very good compared to other methods.

At the same time, the probes are suitable for long-term monitoring activities, with researchers recording signals from the same cells in the brains of animals for the entire duration of a ten-month experiment. Examinations showed that no brain-tissue damage occurred during this time. A further advantage is that the bundles can branch out in different directions, meaning that they can reach multiple brain areas.

Human testing to begin soon

In the study, the researcher used the new electrodes to track and analyse nerve-cell activity in various areas of the brains of rats over a period of several months. They were able to determine that nerve cells in different regions were “co-activated”. Scientists believe that this large-scale, synchronous interaction of brain cells plays a key role in the processing of complex information and memory formation. “The technology is of high interest for basic research that investigates these functions and their impairments in neurological and psychiatric disorders,” Yanik explains.

The group has teamed up with fellow researchers at the University College London in order to test diagnostic use of the new electrodes in the human brain. Specifically, the project involves epilepsy sufferers who do not respond to drug therapy. In such cases, neurosurgeons may remove a small part of the brain where the seizures originate. The idea is to use the group’s method to precisely localise the affected area of the brain prior to tissue removal.

Brain-machine interfaces

There are also plans to use the new electrodes to stimulate brain cells in humans. “This could aid the development of more effective therapies for people with neurological and psychiatric disorders”, says Yanik. In disorders such as depression, schizophrenia or OCD, there is often impairments in specific regions of the brain, which leads to problems in evaluation of information and decision making. Using the new electrodes, it might be possible to detect the pathological signals generated by the neural networks in the brain in advance, and then stimulate the brain in a way that would alleviate such disorders. Yanik also thinks that this technology may give rise to brain-machine interfaces for people with brain injuries. In such cases, the electrodes might be used to read their intentions and thereby, for example, to control prosthetics or a voice-output system.

Source: ETH Zurich

An Ancient Brain Area Processes Numerical Concepts

Photo by Anna Shvets

New research in patients undergoing neurosurgery reveals the unique human ability to conceptualise numbers may be rooted deep within the brain. In good news for those who are stumped by maths, the results of the study by Oregon Health & Science University involving neurosurgery patients suggests new possibilities for tapping into those areas to improve learning.

“This work lays the foundation to deeper understanding of number, math and symbol cognition – something that is uniquely human,” said senior author Ahmed Raslan, MD, professor and chair of neurological surgery in the OHSU School of Medicine. “The implications are far-reaching.”

The study appears in the journal PLOS ONE.

Raslan and co-authors recruited 13 people with epilepsy who were undergoing a commonly used surgical intervention to map the exact location within their brains where seizures originate, a procedure known as stereotactic electroencephalography. During the procedure, researchers asked the patients a series of questions that prompted them to think about numbers as symbols (for example, 3), as words (“three”) and as concepts (a series of three dots).

As the patients responded, researchers found activity in a surprising place: the putamen.

Located deep within the basal ganglia above the brain stem, the putamen is an area of the brain primarily associated with elemental functions, such as movement, and some cognitive function, but rarely with higher-order aspects of human intelligence like solving calculus. Neuroscientists typically ascribe consciousness and abstract thought to the cerebral cortex, which evolved later in human evolution and wraps around the brain’s outer layer in folded grey matter.

“That likely means the human ability to process numbers is something that we acquired early during evolution,” Raslan said. “There is something deeper in the brain that gives us this capacity to leap to where we are today.”

Researchers also found activity as expected in regions of the brain that encode visual and auditory inputs, as well as the parietal lobe, which is known to be involved in numerical and calculation-related functions.

From a practical standpoint, the findings could prove useful in avoiding important areas during surgeries to remove tumors or epilepsy focal points, or in placing neurostimulators designed to stop seizures.

“Brain areas involved in processing numbers can be delineated and extra care taken to avoid damaging these areas during neurosurgical interventions,” said lead author Alexander Rockhill, PhD, a postdoc in Raslan’s lab.

Researchers credited the patients involved in the study.

“We are extremely grateful to our epilepsy patients for their willingness to participate in this research,” said co-author Christian Lopez Ramos, MD, neurosurgical resident at OHSU. “Their involvement in answering our questions during surgery turned out to be the key to advancing scientific understanding about how our brain evolved in the deep past and how it works today.”

Indeed, the study follows previous lines of research involving mapping of the human brain during surgery.

“I have access to the most valuable human data in nature,” Raslan said. “It would be a shame to miss an opportunity to understand how the brain and mind function. All we have to do is ask the right questions.”

In the next stage of this line of research, Raslan anticipates discerning areas of the brain capable of performing other higher-level functions.

Source: Ohio State University

Heart Rate Activity Influences When Infants Speak

Photo by Johnny Cohen on Unsplash

The soft, gentle murmurs of a baby’s first expressions, like little whispers of joy and wonder to doting parents, are actually signs that the baby’s heart is working rhythmically in concert with developing speech.

Jeremy I. Borjon, University of Houston assistant professor of psychology, reports in Proceedings of the National Academy of Sciences that a baby’s first sweet sounds and early attempts at forming words are directly linked to the baby’s heart rate. The findings have implications for understanding language development and potential early indicators of speech and communication disorders.

For infants, producing recognisable speech is more than a cognitive process. It is a motor skill that requires them to learn to coordinate multiple muscles of varying function across their body. This coordination is directly linked to ongoing fluctuations in heart rate.

Borjon investigated whether these fluctuations in heart rate coincide with vocal production and word production in 24-month-old babies. He found that heart rate fluctuations align with the timing of vocalizations and are associated with their duration and the likelihood of producing recognisable speech.

“Heart rate naturally fluctuates in all mammals, steadily increasing then decreasing in a rhythmic pattern. It turns out infants were most likely to make a vocalisation when their heart rate fluctuation had reached a local peak (maximum) or local trough (minimum),” reports Borjon.

“Vocalisations produced at the peak were longer than expected by chance. Vocalisations produced just before the trough, while heart rate is decelerating, were more likely to be recognised as a word by naïve listener,” he said.

Borjon and team measured a total of 2708 vocalisations emitted by 34 infants between 18 and 27 months of age while the babies played with a caregiver. Infants in this age group typically don’t speak whole words yet, and only a small subset of the vocalisations could be reliably identified as words by naïve listeners (10.3%). For the study, the team considered the heart rate dynamics of all sounds made by the baby’s mouth, be it a laugh, a babble or a coo.

“Every sound an infant makes helps their brain and body learn how to coordinate with each other, eventually leading to speech,” Borjon said.

As infants grow, their autonomic nervous system grows and develops. The first few years of life are marked by significant changes in how the heart and lungs function, and these changes continue throughout a person’s life.

The relationship between recognisable vocalisations and decelerating heart rate may imply that the successful development of speech partially depends on infants experiencing predictable ranges of autonomic activity through development.

“Understanding how the autonomic nervous system relates to infant vocalisations over development is a critical avenue of future research for understanding how language emerges, as well as risk factors for atypical language development,” said Borjon

Source: University of Houston

Men More Than Three Times as Likely to Die From a Brain Injury, New Study Shows

Photo by Anna Shvets

A new analysis of mortality data reveals the disproportionate impact of traumatic brain injuries (TBI) on older adults, males and certain racial and ethnic groups. The study, published in the peer-reviewed journal Brain Injury, provides a comprehensive analysis of TBI-related deaths across different population groups across the US in 2021.

The findings indicate that suicides remain the most common cause of TBI-related deaths, followed by unintentional falls, and specific groups are disproportionately affected by these tragedies.

Men, in particular, were found to be most likely to die from a TBI – more than three times the rate of women (30.5 versus 9.4). The reasons observed were multifactorial and could reflect differences in injury severity following a fall or motor vehicle crash, to the interaction of sex and age – with TBI outcomes in men worsening with age, while postmenopausal women fare better than men of similar age.

“While anyone is at risk for getting a TBI, some groups have a higher chance than others of dying from one. We identified specific populations who are most affected. In addition to men, older adults are especially at risk, with unintentional falls being a major cause of TBI-related death. American Indian or Alaska Native people also have higher rates of these fatal injuries,” says lead author Alexis Peterson PhD, of the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention.

“These findings highlight the importance of tailored prevention strategies to reach groups who may be at higher risk and the role healthcare providers can play in reducing TBI-related deaths through early intervention and culturally sensitive care.”

TBI remains a leading cause of injury-related death in the US In 2020, TBIs were associated with around a quarter of all injury-related deaths.

Using data from the National Vital Statistics System, the new analysis identified 69 473 TBI-related deaths among US residents during 2021. The age-adjusted TBI-related mortality rate was 19.5 per 100 000, representing an 8.8% increase from 2020.

Through statistical modeling, the researchers examined the simultaneous effect of multiple factors such as geographic region, sex, race and ethnicity, and age, on TBI-related mortality.

Key findings include:

  • Older adults (75+) had the highest rates of TBI-related deaths, with unintentional falls being the most common cause in this age group.
  • Non-Hispanic American Indian/Alaska Native individuals experienced the highest TBI-related death rate (31.5) compared to other racial and ethnic groups.
  • There were 37,635 TBI-related deaths categorised as unintentional injuries (ie, motor vehicle crashes, unintentional falls, unintentionally struck by or against an object, other).
  • 30,801 were categorized as intentional injuries (ie, all mechanisms of suicide and homicide).
  • Children aged from birth to 17 years accounted for around 4% of TBI-related deaths (2,977).

The authors emphasise the critical role of healthcare providers in preventing TBI-related deaths, particularly with groups at higher risk. “By assessing patients who may be at higher risk for TBI, especially due to falls or mental health challenges, healthcare providers can make timely referrals and recommend culturally tailored interventions to prevent further injury or death,” says Dr Peterson.

Public health efforts should focus on addressing the underlying causes of TBI-related deaths, such as unintentional falls and mental health crises, to help prevent further loss of life. “TBIs remain a significant public health concern, especially among older adults, men, and certain racial and ethnic groups,” says Peterson.  “CDC has proven resources that healthcare providers can use to not only reduce health disparities that increase the risk for TBI but also improve care for anyone affected by a TBI.”

The authors note the COVID-19 pandemic could have influenced TBI-related death trends in 2021. They also acknowledge several limitations of this analysis, including potential misclassification or incomplete documentation of causes on death certificates, which may lead to inaccuracies in estimating TBI-related deaths.

Source: Taylor & Francis Group

Sex Differences in Brain Structure Present at Birth

Photo by Chayene Rafaela on Unsplash

Sex differences in brain structure are present from birth, research from the Autism Research Centre at the University of Cambridge has shown.

While male brains tended to be greater in volume than female brains, when adjusted for total brain volume, female infants on average had significantly more grey matter, while male infants on average had significantly more white matter in their brains.

Grey matter is made up of neuron cell bodies and dendrites and is responsible for processing and interpreting information, such as sensation, perception, learning, speech, and cognition.  White matter is made up of axons, which are long nerve fibres that connect neurons together from different parts of the brain. 

Yumnah Khan, a PhD student at the Autism Research Centre, who led the study, said: “Our study settles an age-old question of whether male and female brains differ at birth. We know there are differences in the brains of older children and adults, but our findings show that they are already present in the earliest days of life.

“Because these sex differences are evident so soon after birth, they might in part reflect biological sex differences during prenatal brain development, which then interact with environmental experiences over time to shape further sex differences in the brain.”

One problem that has plagued past research in this area is sample size. The Cambridge team tackled this by analysing data from the Developing Human Connectome Project, where infants receive an MRI brain scan soon after birth. Having over 500 newborn babies in the study means that, statistically, the sample is ideal for detecting sex differences if they are present.

A second problem is whether any observed sex differences could be due to other factors, such as differences in body size.  The Cambridge team found that, on average, male infants had significantly larger brain volumes than did females, and this was true even after sex differences in birth weight were taken into account.

After taking this difference in total brain volume into account, at a regional level, females on average showed larger volumes in grey matter areas related to memory and emotional regulation, while males on average had larger volumes in grey matter areas involved in sensory processing and motor control.

The findings of the study, the largest to date to investigate this question, are published in the journal Biology of Sex Differences.

Dr Alex Tsompanidis who supervised the study, said: “This is the largest such study to date, and we took additional factors into account, such as birth weight, to ensure that these differences are specific to the brain and not due to general size differences between the sexes.

“To understand why males and females show differences in their relative grey and white matter volume, we are now studying the conditions of the prenatal environment, using population birth records, as well as in vitro cellular models of the developing brain. This will help us compare the progression of male and female pregnancies and determine if specific biological factors, such as hormones or the placenta, contribute to the differences we see in the brain.”

The researchers stress that the differences between males and females are average differences.

Dr Carrie Allison, Deputy Director of the Autism Research Centre, said: “The differences we see do not apply to all males or all females, but are only seen when you compare groups of males and females together. There is a lot a variation within, and a lot of overlap between, each group.”  

Professor Simon Baron-Cohen, Director of the Autism Research Centre, added: “These differences do not imply the brains of males and females are better or worse. It’s just one example of neurodiversity. This research may be helpful in understanding other kinds of neurodiversity, such as the brain in children who are later diagnosed as autistic, since this is diagnosed more often in males.”

The research was funded by Cambridge University Development and Research, Trinity College, Cambridge, the Cambridge Trust, and the Simons Foundation Autism Research Initiative.

Reference
Khan, Y.T., Tsompanidis, A., Radecki, M.A. et al. Sex differences in human brain structure at birth. Biol Sex Differ; 17 Oct 2024; DOI: 10.1186/s13293-024-00657-5

Republished under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Source: University of Cambridge

Study Likely to Change Standard of Care for Deadly Vertebrobasilar Stroke

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

Endovascular therapy (EVT), a minimally invasive surgery performed inside the blood vessels, is 2 ½ times more likely than standard medical management to achieve a positive outcome after vertebrobasilar stroke that affects the back of the brain, including the brain stem. A meta-analysis of four randomised clinical trials, published in The Lancet, was led by UPMC Stroke Institute director Raul Nogueira, MD.

Investigators from the US, Netherlands and China formed a multi-centre collaboration of all four randomised trials of EVT in vertebrobasilar occlusion with data that provides the strongest evidence to date of the benefits of EVT over alternative approaches for complicated vessel obstructions in life-sustaining areas of the brain.

Although vertebrobasilar artery occlusions interrupting blood flow in the back of the brain account for only a small fraction of all ischaemic strokes, they are especially deadly. Without an appropriate intervention, vertebrobasilar strokes lead to high rates of severe disability and mortality that may exceed 70%.

“While the overwhelming benefit of EVT for acute ischaemic strokes due to occlusions of large vessels that supply the anterior brain has been well established, the benefit of this therapy for vertebrobasilar artery occlusion, one of the most devastating forms of stroke, has been more controversial,” said Nogueira, endowed professor of neurology and neurosurgery at the University of Pittsburgh.

To address this uncertainty, the consortium of investigators, called VERITAS, focused on providing more precise, comprehensive and statistically powered estimates of the benefits of EVT with a particular focus on specific patient subgroups of clinical interest.

As the primary coordinating centre for the study, the Pitt team established common variables, definitions and trial specifications that laid the groundwork for a core pooled dataset from the four randomised controlled clinical trials ATTENTION, BAOCHE, BASICS and BEST of EVT for stroke due to vertebrobasilar artery occlusion.

Meta-analysis showed that at three months after the surgery, despite higher rates of brain bleeds with the procedure, EVT significantly reduced patient mortality and overall post-stroke disability, increasing patients’ functional independence. Notably, patients who underwent EVT were nearly 2 ½ times more likely to regain their ability to walk independently compared to patients who received the current medical standard of care, including intravenous thrombolytics.

“The results of the VERITAS collaboration are expected to influence treatment guidelines and impact stroke care globally,” Nogueira said. “We hope that this analysis sets the foundation for improved recovery after vertebrobasilar strokes and helps more people regain their independence after this catastrophic medical event.”

Source: University of Pittsburgh

Books Beat TV When it Comes to Brain Health

…but is that any surprise?

Photo by Nong on Unsplash

It’s that time of the year when most of us get the chance to sit back and enjoy some well-deserved down time. But whether you reach for the TV controller, or a favourite book, your choice could have implications for your long-term brain health, say researchers at the University of South Australia who published their research in the Journals of Gerontology.

Assessing the 24-hour activity patterns of 397 older adults (aged 60+), researchers found that the context or type of activity that you engage in, matters when it comes to brain health. And specifically, that some sedentary (or sitting) behaviours are better for cognitive function than others.

When looking at different sedentary behaviours, they found that social or mentally stimulating activities such as reading, listening to music, praying, crafting, playing a musical instrument, or chatting with others are beneficial for memory and thinking abilities. Yet watching TV or playing video games are detrimental.

Researchers believe that there is likely a hierarchy of how sedentary behaviours relate to cognitive function, in that some have positive effects while others have negative effects.

It’s a valuable insight that could help reduce risks of cognitive impairment, particularly when at least 45% of dementia cases could be prevented through modifiable lifestyle factors.

In Australia, about 411,100 people (or one in every 1000 people) are living with dementia. Nearly two-thirds are women. Globally, the World Health Organization estimates that more than 55 million people have dementia with nearly 10 million new cases each year.

UniSA researcher Dr Maddison Mellow says that not all sedentary behaviours are equal when it comes to memory and thinking ability.

“In this research, we found that the context of an activity alters how it relates to cognitive function, with different activities providing varying levels of cognitive stimulation and social engagement,” Dr Mellow says.

“We already know that physical activity is a strong protector against dementia risk, and this should certainly be prioritised if you are trying to improve your brain health. But until now, we hadn’t directly explored whether we can benefit our brain health by swapping one sedentary behaviour for another.

“We found that sedentary behaviours which promote mental stimulation or social engagement — such as reading or talking with friends — are beneficial for cognitive function, whereas others like watching TV or gaming have a negative effect. So, the type of activity is important.

“And, while the ‘move more, sit less’ message certainly holds true for cardiometabolic and brain health, our research shows that a more nuanced approach is needed when it comes to thinking about the link between sedentary behaviours and cognitive function.”

Now, as the Christmas holidays roll around, what advice do researchers have for those who really want to indulge in a myriad of Christmas movies or a marathon of Modern Family?

“To achieve the best brain health and physical health benefits, you should prioritise movement that’s enjoyable and gets the heart rate up, as this has benefits for all aspects of health,” Dr Mellow says.

“But even small five-minute time swaps can have benefits. So, if you’re dead set on having a Christmas movie marathon, try to break up that time with some physical activity or a more cognitively engaged seated activity, like reading, at some point. That way you can slowly build up healthier habits.”

Source: University of South Australia

T Cells could Ease Brain Injury after Cardiac Arrest

Photo by Mat Napo on Unsplash

Despite improvements in CPR and ambulance response times, only about one in 10 people ultimately survive after out-of-hospital cardiac arrest (OHCA). Most patients hospitalised with OCHA die of brain injury, and no medications are currently available to prevent this outcome. A team led by researchers from Mass General Brigham found that immune cells may play a key role.

Using samples from patients who have had an OHCA, the team uncovered changes in immune cells just six hours after cardiac arrest that can predict brain recovery 30 days later. They pinpointed a particular population of cells that may provide protection against brain injury and a drug that can activate these cells, which they tested in preclinical models. Their results are published in Science Translational Medicine.

“Cardiac arrest outcomes are grim, but I am optimistic about jumping into this field of study because, theoretically, we can treat a patient at the moment injury happens,” said co-senior and corresponding author Edy Kim, MD, PhD, of the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital. “Immunology is a super powerful way of providing treatment. Our understanding of immunology has revolutionised cancer treatment, and now we have the opportunity to apply the power of immunology to cardiac arrest.”

As a resident physician in the Brigham’s cardiac intensive care unit, Kim noticed that some cardiac arrest patients would have high levels of inflammation on their first night in the hospital and then rapidly improve. Other patients would continue to decline and eventually die. In order to understand why some patients survive and others do not, Kim and colleagues began to build a biobank – a repository of cryopreserved cells donated by patients with consent from their families just hours after their cardiac arrest.

The researchers used a technique known as single-cell transcriptomics to look at the activity of genes in every cell in these samples. They found that one cell population – known as diverse natural killer T (dNKT) cells – increased in patients who would have a favourable outcome and neurological recovery. The cells appeared to be playing a protective role in preventing brain injury.

To further test this, Kim and colleagues used a mouse model, treating mice after cardiac arrest with sulfatide lipid antigen, a drug that activates the protective NKT cells. They observed that the mice had improved neurological outcomes.

The researchers note that there are many limitations to mouse models, but making observations from human samples first could increase the likelihood of successfully translating their findings into intervention that can help patients. Further studies in preclinical models are needed, but their long-term goal is to continue to clinical trials in people to see if the same drug can offer protection against brain injury if given shortly after cardiac arrest.

“This represents a completely new approach, activating T cells to improve neurological outcomes after cardiac arrest,” said Kim. “And a fresh approach could lead to life-changing outcomes for patients.”

Source: Mass General Brigham

The Heart has a ‘Brain’ of its Own

Human heart. Credit: Scientific Animations CC4.0

New research from Karolinska Institutet and Columbia University shows that the heart has a mini-brain – its own nervous system that controls the heartbeat. A better understanding of this system, which is much more diverse and complex than previously thought, could lead to new treatments for heart diseases. The study, conducted on zebrafish, is published in Nature Communications.

The heart has long been thought to be controlled solely by the autonomic nervous system, which transmits signals from the brain. The heart’s neural network, which is embedded in the superficial layers of the heart wall, has been considered a simple structure that relays the signals from the brain. However, recent research suggests that it has a more advanced function than that.

Controlling the heartbeat

Scientists have now discovered that the heart has its own complex nervous system that is crucial to controlling its rhythm.

“This ‘little brain’ has a key role in maintaining and controlling the heartbeat, similar to how the brain regulates rhythmic functions such as locomotion and breathing,” explains Konstantinos Ampatzis, principal researcher and docent at the Department of Neuroscience, Karolinska Institutet, Sweden, who led the study.

The researchers identified several types of neurons in the heart that have different functions, including a small group of neurons with pacemaker properties. The finding challenges the current view on how the heartbeat is controlled, which may have clinical implications.

Surprising complexity revealed

“We were surprised to see how complex the nervous system within the heart is,” says Konstantinos Ampatzis. “Understanding this system better could lead to new insights into heart diseases and help develop new treatments for diseases such as arrhythmias.” 

The study was conducted on zebrafish, an animal model that exhibits strong similarities to human heart rate and overall cardiac function. The researchers were able to map out the composition, organisation and function of neurons within the heart using a combination of methods such as single-cell RNA sequencing, anatomical studies and electrophysiological techniques.

New therapeutic targets

“We will now continue to investigate how the heart’s brain interacts with the actual brain to regulate heart functions under different conditions such as exercise, stress, or disease,” says Konstantinos Ampatzis. “We aim to identify new therapeutic targets by examining how disruptions in the heart’s neuronal network contribute to different heart disorders.”

Source: Karolinska Institutet