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Enlisting help from the brain’s protective system may promote treatment of neurodegenerative conditions

Brain’s vascular system holds clues to treating Alzheimer’s, PTSD, cancer

WEST LAFAYETTE, Ind. — A labyrinthine network of blood vessels helps maintain normal health by protecting the human brain from external pollutants. Unfortunately, this natural protection comes with a price: While the maze keeps the brain safe, it is also an obstacle when it comes to treating brain damage or disease.

For hundreds of thousands of individuals with neurodegenerative conditions, including aftershocks of traumatic brain injuries caused by explosions, finding a way through the network can mean a significant improvement in quality of life. life.

Tiffany Lyle, assistant professor of veterinary anatomical pathology at Purdue University College of Veterinary Medicine and is a member of the Purdue University Cancer Research Center, is on a mission to do just that. She’s the first scientist to map changes to the brain’s barrier during lung cancer metastasis, and more recently, she’s created the first comprehensive molecular map of the network. grid associated with blast-induced traumatic brain injury.

Considered the hallmark trauma of modern warfare, blast-induced traumatic brain injury (bTBI) has been implicated in the development of a number of neurodegenerative diseases, including post-traumatic stress disorder, Parkinson’s and Alzheimer’s disease.

“The trauma from the explosion was like a tsunami,” Lyle said. “The initial impact is like the pulsating force of a wave. But the water continues to cause damage as it recedes into the ocean. We need to look at the long-term changes as well as the initial damage.”

Despite the proven link between bTBI and other life-changing conditions, healthcare scientists know little about how the other is caused.

Suspecting that ongoing changes to the brain’s protective circuitry network might play some role, Lyle applied her expertise in fencing to solve the problem by formulating map the immediate and long-term effects of trauma.

From the protective skin layer to the liver’s detoxification function, the human body relies on a number of complex defenses to stay healthy. Regulating what goes in and out, the brain’s defense system, known as the blood-brain barrier, is the tightest barrier in the body.

While this system is essential for normal health, it causes problems for doctors trying to get drugs into the brain. Likewise, a damaged barrier can allow harmful cells to mistakenly enter and can trigger unnecessary chronic immune responses. Understanding how roadblocks change due to trauma, cancer and disease have slowed the progress of targeted drug delivery and quality of care to patients.

Lyle leads the way for the first comprehensive characterization of both the blood-brain and blood-tumor barriers in brain metastases of lung cancer. Secondary brain tumors affect 20%-40% of cancer patients, and because the barrier’s protection remains active, it also prevents therapeutic drugs from reaching any targeted tumors. Efficiently creating a road map through the maze of blood vessels, Lyle was able to detect when and how certain molecular changes take place when the blood-brain barrier turns into the blood-mass barrier. u.

Early research has identified which parts of the blood-tumor barrier structure may provide useful pathways to improve treatment. The next step is to sort out whether and how the barrier can be breached, and Lyle says she and her research team have discovered a correlation between tumors and cell membrane permeability.

“Understanding changes in permeability can help inform when to change membrane permeability first,” says Lyle. “And anything we can do to improve drug delivery improves the quality of life for patients and their families.”

Improving the quality of care for as many people as possible is one reason Lyle expanded her attention from cancer to other conditions affected by blood-brain barrier function. This new study, in collaboration with Riyi Shi, professor of applied neuroscience Mari Hulman George and director of Purdue University’s Center for Paralysis Research, focuses on changes to the post-traumatic stress barrier. single and repeated blast injury and is the first comprehensive molecular map of the vasculature. network associated with traumatic brain injury caused by an explosion.

By looking at single and repeated outbreaks, the study acknowledges another hard truth about bTBI: Because initial symptoms can be mild or seem temporarily confusing, many individuals — including soldiers — passed immediate medical checks and put themselves at risk of being re-injured too soon.

“We know there’s some degree of damage going on in the brain, but we need to determine what changes to blood vessels and the blood-brain barrier might make effective targets for movement,” says Lyle. switch medications or make targeted changes.

Lyle and her team were able to identify both the neuroinflammatory response and changes in the peripheral cell of the barrier, a structural cell that surrounds the capillaries.

“We were able to conclude that pericytes, or the mechanism underlying neuroinflammation, could be a therapeutic target to address the long-term effects of traumatic brain injury,” says Lyle. “This study is an essential first step in understanding the disease process and how to treat it.”

The next step, says Lyle, is to observe changes in the blood-brain barrier after an impact over a longer period of time. These observations will be important in developing prevention and treatment strategies for people recovering from blast-induced traumatic brain injury, she said. In addition, having these maps for blood-brain barrier changes during and after injury could prove valuable in understanding the progression of other neurodegenerative diseases.

Research that changes the world occupies a village

Expertise in veterinary anatomical pathology — the study of disease, especially its causes and effects — is at the heart of Lyle’s research on the blood-brain barrier. Her need for expertise also puts Lyle, a fellow of the Purdue University Cancer Research Center, at the center of a network of collaborative research projects. Purdue University’s Center for Cancer Research is the National Cancer Institute’s Basic Laboratory Cancer Center, one of only seven in the nation.

Innovative approaches to problems can kickstart the scientific process, but the quality of research depends on robust and reproducible model systems. As director of the Histological Research Laboratory, a division of the Center for Comparative Translational Research, Lyle helps scientists from a variety of disciplines turn good ideas into well-researched discoveries.

“In my collaborative work, I take scientists’ findings – be it drug molecules or medical devices – and use what we know about human disease to design a reliable, reproducible, and clinically relevant human model.

This was the case when Yoon Yeo, a biomedical engineer and professor in the Department of Industrial and Physical Pharmaceuticals, created a nanocapsule capable of delivering drugs into solid tumours. After designing and creating the nanocapsule, Yeo teamed up with Lyle to test its effectiveness and toxicity in laboratory models, bringing the technology closer to human systems.

In the recently expanded and remodeled Histology Research Laboratory, Lyle and her staff work with an average of 130 independent researchers annually.

“The lab can help any researcher using animal, insect or plant tissue and need expertise in veterinary pathology to evaluate their discovery,” says Lyle. “Using veterinary pathology in an experimental setting is my passion; it allows me to expand my reach in countless directions.”

The Histology Research Laboratory is a core facility within the Indiana Institute of Clinical and Translational Sciences, a statewide partnership funded by the National Institutes of Health that includes Indiana University and the University of Notre Dame.

About Purdue University

Purdue University is a leading public research institution developing practical solutions to today’s toughest challenges. Ranked 5th among the most innovative universities in the United States by US News & World Report, Purdue delivers world-changing research and extraordinary discovery. Committed to hands-on and online, real-world learning, Purdue provides a transformative education for all. Committed to affordability and accessibility, Purdue froze tuition and most fees at 2012-13 levels, enabling more students than ever to graduate debt-free. See how Purdue is relentlessly pursuing the next giant leap at https://purdue.edu/.

Writer: Christy McCarter, mccarter@purdue.edu

Contact via media: Nickel Monastery, nickela@purdue.edu

Source: Tiffany Lyle, tiffanylyle@purdue.edu



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