(Press-News.org) SAN FRANCISCO—April 19, 2024—For the roughly 1.5 million Americans per year who survive a traumatic brain injury, health outcomes vary widely. Not only can these injuries lead to a loss of coordination, depression, impulsivity, and difficulty concentrating, but they come with an amplified risk for developing dementia in the future.
The glaring absence of treatments for such a widespread condition drove a team of scientists at Gladstone Institutes to uncover, on a molecular level, how traumatic brain injuries trigger neurodegeneration—and just as importantly, how to target that process to prevent long-term damage.
“We set out to address the fundamental question of exactly what happens in the brain after injury to ignite the damaging process that destroys neurons,” says Jae Kyu Ryu, PhD, a scientific program leader in the lab of Katerina Akassoglou, PhD at Gladstone Institutes.
Most traumatic brain injuries come as a result of falls, car crashes, or violent assaults, according to the Centers for Disease Control, but many also stem from sports accidents or certain military operations such as explosions. In each case, the external force is strong enough to move the brain within the skull, causing a significant breakdown in the blood-brain barrier and allowing blood to move in.
“We knew that a specific blood protein, fibrin, was present in the brain after traumatic brain injury, but we didn’t know until now that it plays a causative role in brain damage after injury,” says Ryu, who led the study that appears in the Journal of Neuroinflammation.
Ryu and others in Akassoglou’s lab have long investigated how blood that leaks into the brain triggers neurologic diseases, essentially by hijacking the brain’s immune system and setting off a cascade of harmful, often-irreversible effects. Fibrin, a protein that normally helps blood coagulate, is the culprit.
“Across many neurological diseases, toxic immune responses in the brain are triggered by blood leaks and drive neurodegeneration,” says Akassoglou, a senior investigator at Gladstone and the director of the Center for Neurovascular Brain Immunology at Gladstone and UCSF. “Neutralizing the toxic immune responses in the brain paves the way to new therapies for neurological diseases.”
In diseases such as Alzheimer’s and multiple sclerosis, abnormal leaks in the protective blood-brain barrier allow fibrin to seep into areas responsible for cognitive and motor functions causing neurodegeneration. But in this case, the traumatic brain injury itself causes the blood to leak into the brain. The new study showed, for the first time, that fibrin is responsible for turning good immune cells bad, causing dangerous inflammation and unleashing toxins that kill neurons.
The Gladstone team used state-of-the-art imaging technology to study mouse brains, as well as brains from people who experienced a traumatic brain injury. They also produced three-dimensional imaging of a whole intact mouse brain, showing blood-brain barrier leaks and abundant fibrin in traumatic brain injury. In both mouse and human brains, fibrin was present together with activated immune cells.
“It became clear that fibrin is activating these immune cells,” Ryu says. “We realized that we can prevent the toxic effects if we could block fibrin, but we had to do it in a precise way.”
The team leveraged genetic tools with a specific mutation in fibrin that can block it from activating immune cells without affecting the protein’s beneficial blood-clotting abilities. This is especially critical for traumatic brain injuries, as excessive bleeding into the brain has been known to occur among patients who were taking anticoagulant medications before their injury.
Akassoglou’s lab previously developed a drug, a therapeutic monoclonal antibody, that acts only on fibrin’s inflammatory properties, without adverse effects on blood coagulation. This fibrin-targeting immunotherapy protects from multiple sclerosis and Alzheimer’s disease in mice. A humanized version of this first-in-class fibrin immunotherapy is already in Phase 1 safety clinical trials by Therini Bio.
“It’s exciting to have a therapeutic option to neutralize blood toxicity in neurologic diseases,” Ryu says. “Future studies are needed to test the effects of the fibrin immunotherapy in traumatic brain injury.”
“This study identifies a potential new strategy to diminish the devastating impacts of brain injuries,” says Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease. “Brain injuries can have profound effects on a person’s cognitive abilities, emotional health, and motor skills, touching every part of their life. It will be interesting to explore whether blocking the disease-promoting effects of fibrin can improve the outcome of brain surgeries and reduce disability when implemented after traumatic brain injuries have occurred.”
About the Study
The study, “Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation,” appears in the April 15, 2024, issue of Journal of Neuroinflammation. Authors include Terry Dean, Andrew Mendiola, Zhaoqi Yan, Rosa Meza Acevedo, Belinda Cabriga, Katerina Akassoglou, and Jae Kyu Ryu.
The work was supported by the National Institutes of Health, the Thrasher Research Fund Early Career Award, the National Multiple Sclerosis Society, the Kaganov Scholarship for Excellence in Neuroscience, the Conrad N. Hilton Foundation, the Dolby Family, and the Simon Family Trust.
About Gladstone Institutes
Gladstone Institutes is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. Established in 1979, it is located in the epicenter of biomedical and technological innovation, in the Mission Bay neighborhood of San Francisco. Gladstone has created a research model that disrupts how science is done, funds big ideas, and attracts the brightest minds.
END
A new therapeutic target for traumatic brain injury
Research from Gladstone Institutes reveals that a blood coagulation protein is responsible for initiating toxic inflammation and neuron loss after a major head injury. The findings can inform new treatment strategies for a condition that often presents lo
2024-04-19
ELSE PRESS RELEASES FROM THIS DATE:
Cosmic rays streamed through Earth’s atmosphere 41,000 years ago
2024-04-19
Earth’s magnetic field cocoons our planet from the onslaught of cosmic radiation streaming through space while also shielding us from charged particles hurled outward by the sun. But the geomagnetic field is not stationary. Not only does magnetic north wobble, straying from true north (a geographically defined location), but occasionally, it flips. During these reversals, north becomes south, south becomes north, and in the process, the intensity of the magnetic field wanes.
But there’s also ...
ACP issues clinical recommendations for newer diabetes treatments
2024-04-19
Embargoed for release until 9:00 a.m. ET on Friday 19 April 2024
Embargoed Content from the Annals of Internal Medicine Breaking News Scientific Plenary at Internal Medicine 2024
Annals of Internal Medicine Tip Sheet
@Annalsofim
Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing ...
New insights into the connections between alcohol consumption and aggressive liver cancer
2024-04-19
While heavy drinking is a well-established risk factor for liver cancer, the specific mechanisms by which alcohol contributes to A-HCC remain unclear.
This insightful review, published in Hepatology, provides a comprehensive summary of the pathogenesis, heterogeneity, preclinical approaches, epigenetic and genetic profiles of A-HCC. Compared to other types of liver cancer, A-HCC is often diagnosed at a later stage, when the disease is more advanced. This is partly due to a lack of readily available screening tools for individuals with alcohol-related liver disease (ALD).
"A-HCC is a serious public health concern," ...
Unraveling water mysteries beyond Earth
2024-04-19
The first clue for finding life on other planets is finding liquid water. The moons of Saturn and Jupiter like Enceladus, Ganymede, Europa, and Callisto are suspected of holding oceans of liquid water beneath icy crusts. Similarly, some exoplanets beyond our solar system likely host liquid water, crucial for habitability. But detecting water, when we can’t physically access these celestial bodies, poses challenges. Ice-penetrating radar, a geophysical tool, has proven capable of detecting liquid water ...
Signs of multiple sclerosis show up in blood years before symptoms
2024-04-19
In a discovery that could hasten treatment for patients with multiple sclerosis (MS), UC San Francisco scientists have discovered a harbinger in the blood of some people who later went on to develop the disease.
In about 1 in 10 cases of MS, the body begins producing a distinctive set of antibodies against its own proteins years before symptoms emerge. These autoantibodies appear to bind to both human cells and common pathogens, possibly explaining the immune attacks on the brain and spinal cord that are the hallmark of MS.
The findings were published in Nature Medicine on ...
Ghost particle on the scales
2024-04-19
In the 1930s, it turned out that neither the energy nor the momentum balance is correct in the radioactive beta decay of an atomic nucleus. This led to the postulate of "ghost particles" that "secretly" carry away energy and momentum. In 1956, experimental proof of such neutrinos was finally obtained. The challenge: neutrinos only interact with other particles of matter via the weak interaction that is also underlying the beta decay of an atomic nucleus. For this reason, hundreds of trillions of neutrinos from the cosmos, especially the sun, can pass through our bodies every second without causing any damage. Extremely ...
Light show in living cells
2024-04-19
Observing proteins precisely within cells is extremely important for many branches of research but has been a significant technical challenge - especially in living cells, as the required fluorescent labelling had to be individually attached to each protein. The research group led by Stefan Kubicek at CeMM has now overcome this hurdle: With a method called "vpCells," it is possible to label many proteins simultaneously, using five different fluorescent colours. This automated high-throughput approach, aided by AI-assisted image recognition, opens up entirely new applications in various disciplines, from fundamental cell biology to drug discovery. The study ...
Climate change will increase value of residential rooftop solar panels across US, study shows
2024-04-19
Graphic
Climate change will increase the future value of residential rooftop solar panels across the United States by up to 19% by the end of the century, according to a new University of Michigan-led study.
The study defines the value of solar, or VOS, as household-level financial benefits from electricity bill savings plus revenues from selling excess electricity to the grid—minus the initial installation costs.
For many U.S. households, increased earnings from residential rooftop ...
Could the liver hold the key to better cancer treatments?
2024-04-19
PHILADELPHIA – Liver inflammation, a common side-effect of cancers elsewhere in the body, has long been associated with worse cancer outcomes and more recently associated with poor response to immunotherapy. Now, a team led by researchers from the Abramson Cancer Center and Perelman School of Medicine at the University of Pennsylvania has found a big reason why.
In their study, published today in Nature Immunology, the researchers discovered that cancer-induced liver inflammation causes liver cells to secrete proteins called serum amyloid A (SAA) proteins, which circulate through the body and hinder the ability of T cells—major anticancer weapons of the immune system—to ...
Warming of Antarctic deep-sea waters contribute to sea level rise in North Atlantic, study finds
2024-04-19
Analysis of mooring observations and hydrographic data suggest the Atlantic Meridional Overturning Circulation deep water limb in the North Atlantic has weakened. Two decades of continual observations provide a greater understanding of the Earth’s climate regulating system.
A new study published in the journal Nature Geoscience led by scientists at University of Miami Rosenstiel School of Marine, Atmospheric, and Earth Science, and the National Oceanic and Atmospheric Administration’s Atlantic ...
LAST 30 PRESS RELEASES:
Program takes aim at drinking, unsafe sex, and sexual assault on college campuses
Inability to pay for healthcare reaches record high in U.S.
Science ‘storytelling’ urgently needed amid climate and biodiversity crisis
KAIST Develops Retinal Therapy to Restore Lost Vision
Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response
Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid
Low LDL cholesterol levels linked to reduced risk of dementia
Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients
Almost one in ten people surveyed report having been harmed by the NHS in the last three years
Enhancing light control with complex frequency excitations
New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients
New insight into factors associated with a common disease among dogs and humans
Illuminating single atoms for sustainable propylene production
New study finds Rocky Mountain snow contamination
Study examines lactation in critically ill patients
UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award
Doubling down on metasurfaces
New Cedars-Sinai study shows how specialized diet can improve gut disorders
Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana
PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation
ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy
How VR technology is changing the game for Alzheimer’s disease
A borrowed bacterial gene allowed some marine diatoms to live on a seaweed diet
Balance between two competing nerve proteins deters symptoms of autism in mice
Use of antifungals in agriculture may increase resistance in an infectious yeast
Awareness grows of cancer risk from alcohol consumption, survey finds
The experts that can outsmart optical illusions
Pregnancy may reduce long COVID risk
Scientists uncover novel immune mechanism in wheat tandem kinase
Three University of Virginia Engineering faculty elected as AAAS Fellows
[Press-News.org] A new therapeutic target for traumatic brain injuryResearch from Gladstone Institutes reveals that a blood coagulation protein is responsible for initiating toxic inflammation and neuron loss after a major head injury. The findings can inform new treatment strategies for a condition that often presents lo