A small bump on the head might not seem so bad, especially if compared to more serious injuries that could result from an automobile crash. But how do different impact injuries affect the brain’s cells? Is there a set force or impulse the head can sustain without permanent injury?
Two college football players prepare to collide. Image credit: Flickr Nathan Rupert
Two researchers in Virginia Tech's Department of Biomedical Engineering and Mechanics, Pamela VandeVord and Scott Verbridge, have received a National Science Foundation grant to ask questions such as these and to advance our understanding of how the brain reacts to trauma.
The brain is made up of hundreds of billions of cells. Neurons are typically thought of as the brain’s critical information processors and, therefore, as the most important cell type. However, brain cells known as astrocytes also play a vital role, in maintaining the brain’s equilibrium by helping to keep metabolites, inflammation, and neurodegeneration in check to maintain a healthy environment in the brain. Without support from astrocytes, neurons would not function properly. In fact, astrocytes are thought to be nearly as numerous in the brain as the neurons themselves.
Because of their important supportive role in the brain, interest in studying astrocytes is growing. Virginia Tech researchers have a rich history of important research into the biology of astrocytes and glial cells more broadly. In this new research, VandeVord and Verbridge will focus on the less-studied mechanical properties of these cells, leveraging the department’s well-established strengths in injury biomechanics and translational cancer research.
VandeVord and Verbridge will investigate cellular effects following brain trauma through a unique mechanical lens. Rather than use flat, 2D models, they will use 3D gels to better represent brain-like cellular environments. These innovative 3D models will give the researchers a more precise understanding of how the cells respond to physical trauma such as blunt impacts from car crashes or blasts.
“Tissue-engineered models can advance our understanding of cellular changes in the brain by removing many of the confounding features present in animal models and allowing us to focus on specific cell types or interactions,” said Verbridge, director of research in the Laboratory of Integrative Tumor Ecology. “Even still, the matrix native to the brain is unique. This is one of our greatest challenges in tissue engineering — to recreate a realistic environment outside of the skull to understand the brain’s cells inside the skull.”
This research is at the intersection of engineering and health sciences. Mechanobiology is an emerging interdisciplinary field that focuses on how physical forces and changes in both cellular and tissue mechanical properties contribute to development, physiology, and disease.
Most mechanobiology research on brain development and function focuses on how mechanotransduction, the process through which cells sense and respond to mechanical stimuli by converting them to biochemical signals that trigger specific cellular responses, mediates the signaling and plasticity of neurons. Neuronal plasticity allows for changes in the brain’s neural circuits, which can then amend the structure and function of the brain. Frequently used neurons develop stronger connections, whereas those that are rarely or never used may die.
When people bump their heads, for example, a certain amount of force and strain gets transmitted to the brain. There are so many questions as to how the cells sense those mechanical forces and then how they decide to respond, said VandeVord, who researches complex mechanisms of injury to the brain and is a previous recipient of an undergraduate training grant focused on biomechanics.
“It is presumed these cells can tolerate some level of injury, up to a point,” said VandeVord, associate dean for research and graduate studies in the College of Engineering and director of research in the Traumatic Nerve Technologies Laboratory. “We are curious to find at what point these cells respond negatively to the strain and force and decided to become dysfunctional, changing in ways that become more permanent and degrading the health of the brain.”
The researchers will induce different levels of strain to find the threshold of injury beyond which the strain and force have permanent negative effects on the brain’s cells.
“Two people can get the same injury and it can lead to completely different outcomes,” said Verbridge, who previously received an National Science Foundation CAREER award for brain cancer research. “I come at this research from a broad desire to understand the spectrum of ways these astrocytes can contribute to multiple diseases. The National Science Foundation is giving us the opportunity to explore the more fundamental basic science but in an area that will have broad and meaningful health implications.”
The results of this research could help explain processes of the brain following trauma, particularly as they relate to natural, pathological processes occurring as a consequence of disease or injury, said VandeVord. A better understanding of trauma’s impact on the brain’s functionality and health could have significant implications for designing novel therapies to treat traumatic brain injuries.
Source: VirginiaTech