Day: August 5, 2025

Categories : NeurologyTags :

How the Brain Controls Its Blood Volume

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Inhibitory neurons and astrocytes hold the key to sharper functional brain imaging –

Image of an astrocyte, a subtype of glial cells. Glial cells are the most common cell in the brain. Credit: Pasca Lab, Stanford University NIH support from: NINDS, NIMH, NIGMS, NCATS

Researchers at the Center for Neuroscience Imaging Research within the Institute for Basic Science (IBS) have uncovered a two-step mechanism by which the brain regulates blood volume – a breakthrough with significant implications for how scientists understand and interpret functional magnetic resonance imaging (fMRI).

At the core of this study are somatostatin-expressing interneurons (SST neurons), a specialised type of inhibitory neuron. Among all neurons in the brain, approximately 15% are inhibitory neurons, but the role of these neurons in regulating cerebral blood volume has not been clearly elucidated in previous studies, with most of earlier research mainly focusing on the excitatory neurons. The new study by the IBS team sheds light on how inhibitory neurons interact with astrocytes, a type of support cell, to precisely control blood vessel dilation in the brain.

To unravel this complex process, the research team developed mouse models (e.g., SST-ChR2, SST-hM4Di) that allowed selective activation or inhibition of SST neurons. The researchers also used advanced neuroscience techniques in these mice. Specifically, they applied optogenetics and chemogenetics to precisely control the activity of these neurons. To observe the cellular and vascular responses, the team employed calcium imaging to visualise astrocyte activity, electrophysiology to measure neural signals, and intrinsic optical imaging (OIS) alongside ultra-high-field functional MRI (fMRI) to track blood volume dynamics with high spatial and temporal resolution.

Through these experiments, the team uncovered a two-step mechanism of vasodilation. In the early phase, SST neurons, when activated, released nitric oxide (NO) – a powerful vasodilator that triggered rapid and widespread expansion of nearby blood vessels. This was followed by a late phase, in which astrocytes became activated and induced slower, more localised vasodilation, especially during periods of prolonged sensory stimulation.

Figure 1. Somatostatin neurons regulate astrocytes surrounding cerebral blood vessels, enabling more precise delivery of blood volume to specific brain regions, thereby enhancing the spatial accuracy of neurovascular responses. Credit: Institute for Basic Science

Notably, when SST neurons were silenced, the layer-specific precision of blood volume signals observed in fMRI was lost – a finding that links cellular activity directly to spatial specificity in imaging data.

“This two-step mechanism involving inhibitory neurons and astrocytes helps explain why high-resolution fMRI can distinguish activity between different layers of the brain cortex,” the researchers explained. “Our study fills a major gap in understanding how neural signals are translated into the blood volume changes we measure in brain imaging.”

The team also overcame several technical challenges – including distinguishing overlapping signals and timing differences – by integrating multiple imaging techniques and running extensive repeat experiments to validate the causal link between SST neuron activity and vascular responses.

Their findings not only advance basic knowledge of neurovascular coupling, but also open new avenues for investigating neurological and psychiatric conditions in which SST neuron function is impaired, such as Alzheimer’s disease, depression, and autism. The group plans to study disease-model mice to identify how disruptions in this neuron–astrocyte–vascular pathway affect blood volume, brain function, and fMRI signals.

Ultimately, this research lays the groundwork for improving the accuracy of brain imaging interpretation and may lead to better diagnostic and therapeutic strategies for brain disorders.

Source: Institute for Basic Science

Categories : Immune System Respiratory DiseasesTags :

Study Reveals Trained Immunity May Cause Lung Damage

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Discovery could help explain why some people are more vulnerable to lung damage during severe inflammation

Photo by Anna Shvets

Trained immunity – a process being explored in vaccine and therapy development to boost immune defences – appears to be counterproductive in certain contexts, researchers at McGill University and the Research Institute of the McGill University Health Centre (The Institute) have found.

Trained immunity is when the body’s first line of defence remembers past threats and becomes more reactive, responding more strongly to future infections even if they are different, by changing immune cells’ behaviour.

In an earlier study, the researchers had determined beta-glucan, a molecule found in the cell walls of fungi like yeast and mushrooms, can reduce lung damage during influenza infection. That study had focused on beta-glucan’s impact on neutrophils.

However, in a new study, published in the journal eLife, the team found exposure to beta-glucan can reprogram alveolar macrophages in a way that worsens lung damage during severe inflammation caused by viral or bacterial products. These cells help keep the lungs clean by clearing out dust, debris and pathogens.

“To date, most trained immunity research has focused on circulating immune cells that arise from the bone marrow,” said lead author Renaud Prével, a postdoctoral fellow at the Meakins-Christie Laboratories at The Institute. “We wanted to explore whether beta-glucan could induce trained immunity in alveolar macrophages, and whether that might be helpful or harmful.”

The researchers exposed mice to beta-glucan, which is known to trigger trained immunity and is found in some health supplements. A week later, the mice were exposed to signals that mimic severe viral or bacterial infections with sepsis-like phenotype. Using high-resolution microCT scans and fluid analysis, they found that mice given beta-glucan developed significantly more severe lung damage compared to the untreated control group.

To confirm the immune cells were causing the damage, researchers removed them from the mice, and the inflammation went away. When they put trained alveolar macrophages into other mice, the inflammation came back. The cells showed signs of immune training, but surprisingly, this didn’t happen through the usual immune pathways. It needed signals from infections and help from other immune cells.

“Our study shows that immune memory in the lungs is more dynamic than previously thought,” said senior author Maziar Divangahi, Professor of Medicine at McGill and Associate Director of the Meakins-Christie Laboratories. “This could help explain why some individuals develop more severe lung inflammation, especially in settings like sepsis.”

Source: McGill University

Categories : AgeingTags :

New Study Highlights the Hidden Risk of Polypharmacy for Older Adults

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Photo by Kampus Production

Inappropriate polypharmacy – the excessive or unnecessary use of multiple medications – is a major driver of emergency hospital admissions among adults aged 65 and over, according to a new study from the Department of Life Sciences at the University of Bath.

The researchers hope their findings will pave the way for the development of a digital tool – such as an app – to proactively identify older adults at risk of medication-related harm and intervene before a hospital visit becomes necessary.

The study, published in Age and Ageing, is the first of its kind to use data-driven methods to explore how potentially inappropriate polypharmacy contributes to short-term hospitalisation in older adults. With this population growing rapidly and facing increased risks of complications from being hospitalised, the findings reinforce concerns in geriatric care over the dangers of overprescribing.

The hidden dangers of overprescribing

Older adults often take multiple medications to manage chronic conditions such as diabetes, hypertension and arthritis. This can lead to prescribing cascades, where side effects from one drug are treated with additional medications, creating a cycle of escalating complexity and risk.

For instance, a patient might be prescribed a drug for pain management, develop high blood pressure as a side effect and then receive another medication to manage that new symptom. Over time, this can lead to a complex web of prescriptions, carrying the risk of harmful interactions.

PhD researcher Robert Olender, who led the study under the supervision of Dr Prasad Nishtala (primary supervisor, from the Department of Life Sciences) and Dr Sandipan Roy (secondary supervisor, from the Depatment of Mathematics) from Bath, said: “With more older adults on complex drug regimens, we need proactive ways to reduce preventable emergency hospitalisations.”

Though the new research is focused on data from the UK, polypharmacy among older adults is known to be a growing problem globally, with studies from countries that include the US, Australia, New Zealand and across Europe consistently linking polypharmacy to increased risks of hospitalisation, adverse drug reactions and reduced quality of life.

In an earlier study based on a New Zealand dataset, also carried out by the team at Bath, a strong correlation was found in older people between a high drug burden, alcohol consumption and smoking with an increased risk of 30-day hospitalisations.

Using machine learning to predict hospitalisation

The study used a large UK dataset to develop three machine learning models capable of predicting 30-day emergency hospitalisation in older adults with around 75% accuracy.

A key variable in these models was the Drug Burden Index (DBI), which measures the cumulative effect of medications with sedative and anticholinergic properties. Anticholinergics are a class of drug used to treat various chronic conditions such as dementia, depression, urinary incontinence and chronic obstructive pulmonary disease (COPD).

The cumulative effects of these drugs consistently emerged as one of the strongest predictors of a person being at risk of emergency hospitalisation. Other predictors included impaired mobility, a history of fractures and falls, smoking and excessive alcohol consumption.

What makes this study unique is its focus on a previously underexplored dataset and age group, offering new insights into a long-standing issue. While the dangers of polypharmacy are well known, this research highlights the link between polypharmacy and short-term hospitalisation. It also lays the groundwork for a potential tool to identify at-risk patients and guide them toward safer care.

From research to real-life impact

The research team envisions an app for clinicians that uses a simple questionnaire to assess a patient’s risk of hospitalisation. Questions might include current prescriptions, lifestyle factors (e.g. smoking and alcohol use) and chronic conditions like cancer or hypertension. The tool would then generate a risk score, allowing clinicians to make informed decisions in real time.

Such a tool could serve as a low-cost, high-impact intervention to keep patients safe and create savings for the NHS. By identifying high-risk patients early, clinicians may adjust medication regimens, encourage physical activity or address modifiable lifestyle factors – simple steps that could significantly reduce an individual’s risk of an emergency hospital admission.

While the app could be developed relatively quickly, integrating it into clinical workflows would require regulatory approval and trials. However, the potential benefits – fewer hospital admissions, improved patient safety, and reduced healthcare costs – make this a compelling investment, the researchers believe.

The team hopes such a tool would raise awareness among healthcare professionals, particularly those in primary care, community pharmacies and hospices, where early intervention could help prevent emergency hospital admissions.

Source: University of Bath

Categories : VaccinesTags :

A Revolutionary ‘Single Shot’ Malaria Vaccine Delivery System

On By ModernMedia

Oxford researchers have developed programmable microcapsules to deliver vaccines in stages, potentially eliminating the need for booster shots and increasing immunisation coverage in hard-to-reach communities.

Photo by Mufid Majnun on Unsplash

A team of scientists at the University of Oxford has developed an innovative vaccine delivery system that could allow a full course of immunisation – both initial and booster doses – to be delivered in just one injection. In preclinical trials, the technology provided strong protection against malaria, matching the efficacy of traditional multi-dose vaccination regimens.

Luca Bau, Senior Researcher from the Institute of Biomedical Engineering, said: ‘Reducing the number of clinic visits needed for full vaccination could make a major difference in communities where healthcare access is limited. Our goal is to help remove the barriers that stand in the way of people benefiting from life-saving medical innovations.’

The findings offer hope for a simpler, more effective approach to immunisation, particularly in regions where access to follow-up healthcare is limited.

A new weapon in the fight against preventable diseases

The research, published in Science Translational Medicine, addresses a major challenge in global health: ensuring people return for all required vaccine doses. Missed boosters are one of the biggest barriers to achieving full immunisation, leaving millions vulnerable to preventable infectious diseases.

To tackle this, the Oxford team developed tiny biodegradable capsules that can be co-injected with the first vaccine dose and programmed to release the booster dose weeks or months later. In a mouse model, this “single shot” strategy using the R21 malaria vaccine protected against the disease nearly as effectively as the standard two-dose schedule.

Simple, scalable, and injectable

The microcapsules are made using a patented chip-based microfluidics system that is compatible with existing pharmaceutical production methods. This means the technology can be scaled up rapidly for clinical use and eventual deployment in the field.

Romain Guyon, Post-Doctoral Scientist, inventor of the technology and the lead author on the study said: ‘Our approach solves three of the biggest problems in delayed vaccine delivery: how to make it programmable, injectable, and scalable. The microcapsules are precisely engineered to act as a tiny, timed-release vault, allowing us to dictate exactly when the booster dose is released. We believe this could be a gamechanger not just for malaria but for many other vaccines requiring multiple doses or other complex therapeutic regimens.’

The capsules are made from an approved biodegradable polymer (PLGA) and filled with the R21 malaria vaccine. Once injected, the priming dose works immediately, while the capsules burst within the body to release the booster after a set delay. Researchers were able to fine-tune this delay from two weeks to several months.

Looking ahead

The team is now working to adapt the manufacturing process in preparation for early-stage human trials, attracting interest from pharmaceutical partners and global health organisations.

Anita Milicic, Associate Professor at the Jenner Institute, Nuffield Department of Medicine, said: ‘This is the exciting first step in proving that it is possible to administer the full immunisation complement through a single injection. We now turn to the next challenge: adapting and refining the approach for translation into the clinic, towards ultimately delivering a real-world impact.’

If successful, this technology could revolutionise vaccination campaigns, particularly in areas where logistics and healthcare access make booster schedules impractical. With 20.5 million children missing routine vaccinations in 2022 alone, the implications of a truly single-dose vaccine could be enormous.

Source: University of Oxford

Categories : PaediatricsTags :

How Much Infants Cry is Mostly Down to Genetics

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Photo by William Fortunato

How much an infant cries is largely steered by their genetics and there is probably not much that parents can do about it. This has been shown in a new Swedish twin study from Uppsala University and Karolinska Institutet in which researchers investigated how genetics and environment influence infants’ crying duration, sleep quality and ability to settle during the first months of life.

The study, which was recently published in JCPP Advances, is based on questionnaire responses from parents of 1000 twins spread across Sweden. The parents were asked questions about their children’s sleep, crying and ability to settle when the twins were two months old and then again at five months old. The researchers were interested in finding out how genetics and environment influence these behaviours during the first months of life – something that no study has done before.

The clearest results were seen when the researchers analysed how long the children cried per day.

“What we found was that crying is largely genetically determined. At the age of two months, the children’s genetics explain about 50 per cent of how much they cry. At five months of age, genetics explain up to 70% of the variation. For parents, it may be a comfort to know that their child’s crying is largely explained by genetics, and that they themselves have limited options to influence how much their child cries,” says Charlotte Viktorsson, postdoctoral fellow in psychology and lead author of the study.

The parents who participated in the study were asked how long their children cried, how often they woke up at night, and how long it took until they settled. There was large individual variation between the children. For example, some children could wake up a total of up to 10 times per night. The figures below show averages.

2 months:
Crying duration (per 24 hours): about 72 minutes
Wakeups: 2.2 times per night
Time until settled: about 20 minutes

5 months:
Crying duration (per 24 hours): about 47 minutes
Wakeups: 2.1 times per night
Time until settled: about 14 minutes

The remaining percentage that cannot be explained by genetics was explained by what the researchers call ‘unique environment’ – factors in the children’s environment or life situation that are unique to each child and cannot be identified precisely from the questionnaire responses.

Charlotte Viktorsson is the lead author of the study that investigated how genetics and environment influence infants’ crying, sleep, and ability to settle during the first months of life. Photo: Mikael Wallerstedt

Twin studies reveal the importance of genetics

The participants were recruited by letter, which was sent to families with twins aged 1–2 months. These families were identified from the population register. To be able to capture how much of a behaviour is genetically determined, the researchers compared identical (monozygotic) twins with fraternal (dizygotic) twins. The advantage of studying twins is that they share important factors such as home environment, family situation, and socio-economic status. If identical twins become more similar to each other than fraternal twins in terms of a certain trait, such as how much they cry, it is seen as an expression of the importance of genetics for that trait.

The environment plays a role in infants’ time until settled

Using the same method, the researchers also analysed the number of times the children woke up at night. Here, genetics played less of a role. The number of awakenings during the night was mainly influenced by environmental factors, which can include sleep routines and the environment in which the child sleeps

In the questionnaire, the parents were also asked to state how long it took from the child being put to bed until they were asleep.

“How rapidly the infant settles was primarily due to the environment at 2 months of age, but by 5 months, their genetics had gained some significance. This reflects the rapid development that occurs in infants, and may indicate that parents’ efforts in getting their child to settle may have the greatest impact in the first months,” says Charlotte Viktorsson, who led the study.

However, it is difficult to draw conclusions about which interventions are effective based on this type of observational study.

“Although we cannot see which specific environmental factors influence the number of awakenings during the night, or how long it takes until the child settles, this study points out a direction for future studies with a focus on sleep routines,” she says.

The researchers have followed the twins up to 36 months of age, allowing them to see how sleep and crying change as the children get older. The current study is thus the first in order based on this data.

Source: Uppsala University