By: Brandon Lucke-Wold
Growing up in Colorado Springs, Colorado, where there are both an Army and an Air Force base, I had multiple family friends and acquaintances in the military. Several of my friends had parents who were injured during combat or developed posttraumatic stress disorder after deployment. My friends described how difficult it was for their parents to deal with the injuries and more importantly that little was available in terms of treatment to help with the symptoms. These stories and interactions with family friends at a young age helped spark my interest in improving care for our nation’s warfighters. As I advanced through college and my M.D./Ph.D. program, several of my friends came back from deployment and began sharing stories about injuries obtained during combat or training, or their struggles with posttraumatic stress disorder.
Blast traumatic brain injury has been described by the Department of Defense as the “signature injury” of modern warfare. After a blast traumatic brain injury, warfighters often experience multiple progressive symptoms including mood disorders, headaches, and seizures. Unfortunately, few treatments are available for these symptoms following blast exposure, and even fewer treatments are available to prevent the progression of neurodegenerative disease. I found a laboratory at West Virginia University devoted to finding new treatments for blast traumatic brain injury where I could conduct my research. Charles Rosen, M.D., Ph.D., chairman of the Department of Neurosurgery, and Jason Huber, Ph.D., expert in blood brain barrier disruption, co-mentor me for the projects in the laboratory.
We employ multiple approaches to understand blast traumatic brain injury, including a blast traumatic brain injury rodent model as well as assessment of postmortem tissue from warfighters. Recent findings have implicated oxidative stress, neuroinflammation, and endoplasmic reticulum stress in the progression of symptoms and neurodegeneration following blast exposure. As we learned more about the progression of changes within the brain, we began developing targeted treatment approaches. Fortunately, we have found key pharmaceutical compounds that appear promising in preclinical models of traumatic brain injury. The endoplasmic reticulum stress and oxidative stress modulators not only improved pathologic outcomes, but more importantly they improved behavioral performance and prevented cognitive decline.
Based on these exciting discoveries, we are branching into the realm of human research. We are currently collaborating with physician and physical therapy colleagues to get a better understanding of symptoms experienced by warfighters returning from combat. After these symptoms are better characterized, we plan to employ both pharmaceutical and cognitive behavioral approaches to improve symptoms following blast exposure and, hopefully, limit the severity of posttraumatic stress disorder. We are also investigating a series of supplements that can be used to prevent the progression from acute brain injury to chronic neurodegeneration, such as chronic traumatic encephalopathy.
The Graduate Student Fellowship from the American Association of Pharmaceutical Scientists Foundation helps make this work possible. I hope to continue improving care for our nation’s warfighters as a neurosurgeon scientist throughout my career.