Preventing Brain Damage in Preterm Babies
“As a neonatologist and neuroscientist, it’s frustrating that we don’t have any treatments to counteract the harmful effects of bleeding in the developing brain, even though we know it often leads to lasting problems,” says Petersen, director of the Neuro-Intensive Care Nursery at UC San Francisco (UCSF), associate professor of pediatrics at UCSF, and a visiting scientist at Gladstone Institutes. “Adding to this frustration, we’ve had very little understanding — until now — of why and how this bleeding is so closely tied to the long-term neurological issues these babies often face.”
In a study that appears in Proceedings of the National Academy of Sciences (PNAS), Petersen and an interdisciplinary team of physicians and scientists from Gladstone and UCSF shed light on this vexing medical condition, showing for the first time that a blood protein called fibrin blocks an essential biological process that drives brain development in early life.
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Discovery of How Blood Clots Harm Brain and Body in COVID-19 Points to New Therapy
In a study that reshapes what we know about COVID-19 and its most perplexing symptoms, scientists have discovered that the blood coagulation protein fibrin causes the unusual clotting and inflammation that have become hallmarks of the disease, while also suppressing the body’s ability to clear the virus. Importantly, the team also identified a new antibody therapy to combat all of these deleterious effects.
Published in Nature, the study by Gladstone Institutes and collaborators overturns the prevailing theory that blood clotting is merely a consequence of inflammation in COVID-19. Through experiments in the lab and with mice, the researchers show that blood clotting is instead a primary effect, driving other problems—including toxic inflammation, impaired viral clearance, and neurological symptoms prevalent in those with COVID-19 and long COVID.
“Knowing that fibrin is the instigator of inflammation and neurological symptoms, we can build a new path forward for treating the disease at the root,” says Katerina Akassoglou, PhD, a senior investigator at Gladstone and the director of the Center for Neurovascular Brain Immunology at Gladstone and UC San Francisco. “In our experiments in mice, neutralizing blood toxicity with fibrin antibody therapy can protect the brain and body after COVID infection.”
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A New Therapeutic Target for Traumatic Brain Injury
Jae Kyu Ryu, left, and Zhaoqi Yan, right, collaborate in the Gladstone lab of Katerina Akassoglou.
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.
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How Blood That Leaks into the Brain Makes Immune Cells Toxic
“Our study answers, for the first time in a comprehensive way, how blood that leaks into the brain hijacks the brain’s immune system to cause toxic effects in brain diseases,” said Akassoglou, who is also director of the Center for Neurovascular Brain Immunology at Gladstone and a professor of neurology at UC San Francisco (UCSF). “Knowing how blood affects the brain could help us develop innovative treatments for neurological diseases.”
Read the full article here.
Nature Immunology Selected Our Image For The July 2023 Volume 24 Cover
Katerina Akassoglou and colleagues provide single-cell RNA-sequencing and phosphoproteome analyses of CNS microglia and macrophages in response to blood proteins including activated complement and fibrin. Their findings point to potential therapeutic targeting of microglia activation by immune and vascular signals.
