Trending...
- California: With new laws and 800 new arrests, CHP keeps taking down organized retail theft operations statewide
- Small-Firm Leaders Must Prioritize High-Impact Tasks to Prevent Burnout: New Article in AT
- Ktrowe Digital Asset Center Enhances Risk Management and System Transparency
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 long-term health challenges.
SAN FRANCISCO, April 19, 2024 /PRNewswire/ -- 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.
More on The Californer
"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 UC San Francisco. "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.
More on The Californer
"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.
Media Contact
Kelly Quigley
Gladstone Institutes
Director of Science Communications and Media Relations
[email protected]
SOURCE Gladstone Institutes
SAN FRANCISCO, April 19, 2024 /PRNewswire/ -- 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.
More on The Californer
- California: Paw and order: four new K-9 teams join CHP to increase public safety statewide
- California: Governor Newsom announces multiple clemency actions
- California: Governor Newsom proclaims Veterans Day
- Governor Newsom fights for Californians' access to food benefits while Trump basically says "THE POOR MUST STARVE!"
- California and Fresno unite to tackle unsheltered homelessness through new cooperative agreement
"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 UC San Francisco. "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.
More on The Californer
- AI Trading Robots Deliver +159% Annualized Returns and 90% Win Rates on Top ETFs
- California: Governor Newsom proclaims Native American Heritage Month
- Wareham Development Announces Leadership Roles in Community Relations and Marketing Communications
- Kaplan Morrell Law Firm Represents Former NHL Player in Workers' Compensation Case Drawing National Attention
- Long Beach Airport to Undergo $37 Million Passenger Concourse Modernization
"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.
Media Contact
Kelly Quigley
Gladstone Institutes
Director of Science Communications and Media Relations
[email protected]
SOURCE Gladstone Institutes
Filed Under: Business
0 Comments
Latest on The Californer
- Introducing Garment Saver's Planet-Friendly Makeup Guard
- Environmental leaders, fire practitioners applaud California's efforts to expand beneficial fire this Fall
- Boston Industrial Solutions' Natron® DC Series Ink Has Had an Upgrade!
- Long Beach Seeks Volunteers for 2026 Homeless Point in Time Count
- Colony Ridge Proudly Supports the All Ears! 2025 Sporting Clays Tournament
- Jacob Emrani Nominated for LA Executive Award
- Massively parallel implementation of nonlinear functions using an optical processor
- California: Governor Newsom proclaims Alzheimer's Disease Awareness Month
- World-leading economy and climate solutions: California's emissions drop in 2023, driven by clean transportation
- Kansas City Steak Company Shares the Return of Their Holiday Gift Box
- Shiba Delivery Hits 100 Movers — and We're Just Getting Started
- Dr Hill Launches The Only Veterinary-Formulated Activated Charcoal Flavored Gel for Pet Emer
- John Grace Founder of Investor's Advantage Corporation Joins Tom Hegna on the Podcast "Financial Freedom with Tom Hegna"
- California: Retail theft crackdown keeps delivering results: 25,675 arrests and $190 million in recovered stolen goods
- Dr. Jay A. Johannigman Delivers Lecture at the John R. Border Memorial Lectureship in Buffalo
- Powering the Next Frontier of the $1 Trillion Space Economy: Ascent Solar Technologies (N A S D A Q: ASTI)
- Taikan's T-V856S VMC Earns Prestigious 2025 Vogel Global Pioneer Award
- Flick Truck Accident Law Joins the Commercial Vehicle Safety Alliance to Strengthen Truck Safety Advocacy
- PebblePad Announces Global Partnership with Inside Higher Ed and Times Higher Education
- Jacko Law Group Named Among Best Law Firms® for Corporate Law in San Diego