Tag: brain injury

Categories : Emergency Medicine NeurologyTags :

T Cells could Ease Brain Injury after Cardiac Arrest

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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

Categories : NeurologyTags :

Fruit Fly Study Shows Role of Age and Sex-related Head Injury Outcomes in Females

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A new study has discovered that even very mild, non-lethal head injuries early in life can lead to neurodegenerative conditions later in life upon ageing. Using fruit flies as a model, the researchers found that chronic immune suppression after mating might make female fruit flies susceptible to delayed brain deterioration following early-life head injuries, which may lead to insights for humans.

The study, published as a Reviewed Preprint in eLife, is described by the editors as fundamental work that advances our understanding of how sex-dependent responses to traumatic brain injury occurs. The work, by a team at Emory University provides what they call compelling results showing the immune and reproductive pathways that may contribute to these differences.

Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration later in life. However, identifying a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegeneration is challenging, and it remains unclear as to how sex and age compound the outcomes.

“With their short lives, fruit flies allow scientists to track brain-injury-related changes across their entire lifespan,” says lead author Changtian Ye, a graduate student in the Emory Neuroscience Program, and a member of senior author James Zheng’s lab, at the Emory University School of Medicine. “We recently developed a fruit fly model of mild traumatic brain injury that allows us to deliver mild headfirst impacts and then track what happens in male and female flies from the moment of injury to the occurrence of brain impairments later in life.”

Using their model, Ye and colleagues monitored the impact of mild traumatic brain injury on the flies’ behaviour. Whilst injury initially caused minimal acute deficits in the flies, it led to more profound brain-associated behavioural deficits and degeneration later in life, and these conditions worsened with age. Additionally, they were disproportionately elevated in females, affecting their climbing speed and ability, and leading them to have more damaged brain tissue than their male counterparts.

The researchers also found that female flies that had mated had worse outcomes than unmated (virgin) flies. They identified a protein called ‘sex peptide’ – which is transferred to the female reproductive tract through semen during mating – as a key player in making these flies more susceptible to the harmful effects of brain injury.

“Our analysis of the flies’ RNA data suggested that the chronic suppression of innate immune defence networks in mated females exposed to sex peptide makes them disproportionately vulnerable to neurodegeneration after mild head trauma,” Ye explains.

Together, the findings support the idea that a head injury can pose a major threat for brain health, even if it is mild, and that females can be disproportionately affected. The authors say that additional studies are now needed to determine if similar processes occur in other species.

“Our work establishes a causal relationship between early head trauma and late-life neurodegeneration, emphasising sex differences in injury response and the impact of age during and after injury,” concludes senior author James Zheng, Principle Investigator at the Zheng Lab, Emory University School of Medicine. “It will be interesting to understand if this relationship occurs in other organisms, and to dissect the genetic components and molecular players involved in the sex-different development of neurodegenerative conditions following mild head trauma.”

Source: eLife

Categories : Injury & TraumaTags :

Students Develop an AI Tool that Predicts Survival of Brain Injury in ICU

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Photo by Anna Shvets on Pexels

A pair of postgraduate students have developed a ground-breaking method for predicting which intensive care unit (ICU) patients will survive a severe brain injury. The two researchers combined functional magnetic resonance imaging (fMRI) with state-of-the art machine learning techniques to tackle one of the most complex issues in critical care. They describe the new technology in the Journal of Neurology.

Whether it is the result of a stroke, cardiac arrest or traumatic brain injury, lives can forever be changed by a serious brain injury. But the potential of a good recovery is highly uncertain.

The University of Western Ontario researchers, Matthew Kolisnyk and Karnig Kazazian, are PhD candidates at Schulich School of Medicine & Dentistry in the lab of neuroscientist Adrian Owen.

“For years we’ve lacked the tools and techniques to know who is going to survive a serious brain injury,” said Owen.

An interdisciplinary team of researchers from Western, in collaboration with neurologists at London Health Sciences Centre and Lawson Health Research Institute sought to find a solution to this problem. They were led by Loretta Norton, a psychology professor at King’s University College at Western, who was one of the first researchers in the world to measure brain activity in the ICU.

The team measured brain activity in 25 patients at one of London’s two ICUs in the first few days after a serious brain injury and tested whether it could predict who would survive and who would not.

“We previously found that information about the potential for recovery in these patients was captured in the way different brain regions communicate with each other,” said Norton. “Intact communication between brain regions is an important factor for regaining consciousness.”

The breakthrough occurred when the team realized they could combine this imaging technique with an application of AI known as machine learning. They found they could predict patients who would recover with an accuracy of 80 per cent, which is higher than the current standard of care.

“Modern artificial intelligence has shown incredible predictive capabilities. Combining this with our existing imaging techniques was enough to better predict who will recover from their injuries,” said Kolisnyk.

While encouraging, the researchers say the prediction was not perfect and needs further research and testing.

“Given that these models learn best when they have lots of data, we hope our findings will lead to further collaborations with ICUs across Canada,” said Kazazian.

Source: University of Western Ontario

Categories : UncategorizedTags :

Brain Swelling Has an Unexpected Protective Effect

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Animal studies have shown that swelling in the brain can protect it in the longer term. Dangerous brain activity can take place after a brain injury (such as from blunt trauma), where neural network activity can surge to dangerous levels, resulting in seizures and tissue injury for months or years after the original injury. Swelling may reduce this long-term effect, an unexpected protective benefit.

At the University of Utah, Punam Sawant-Pokam, PhD, and KC Brennan, MD, investigated the effects of cerebral injury and swelling. They examined the brains of mice subjected to injury with a range of advanced tools for brain recording and electrical activity, 

When observations were made 48 hours after injury, when maximum swelling usually appears, untreated mice brains showed swollen neurons but their neuronal activity had surprisingly dropped. Mice that were given drugs to reduce swelling showed that the neurons continued to show over-activity.

“This data prompts a pretty big reconsideration of how we view edema after brain injury,” Brennan said. “When oedema is about to cause death, it is the number one priority. We’re not saying this is not true. But we’re opening up more nuance to the phenomenon in a way that might allow us to eventually get to more specific treatments and better outcomes.

“It’s very exciting to know that neuronal oedema is not only reducing cellular excitability, it’s also protecting the brain from dangerous network events,” Sawant-Pokam said.

The findings suggest that patients could benefit from more targeted approaches to dealing with cerebral oedema.

Source: Medical Xpress