Concussions and repetitive head trauma have long been considered unfortunate but accepted consequences of high-contact sports like football, boxing, and hockey. These injuries were often viewed simply as a part of the physical cost of athletic competition. However, growing scientific understanding has now shown that the effects of head injuries extend far beyond the field of play and can have serious long-term health consequences. Increasing evidence has linked repeated brain trauma to neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), Alzheimer’s disease, and Parkinson’s disease, and researchers are working to understand the underlying mechanisms connecting brain trauma to these conditions.
At the heart of these discoveries is a new perspective on how head injuries may activate latent viruses already residing in the brain, setting off a cascade of biological events that contribute to long-term damage. These revelations are prompting major shifts in sports safety measures, including modifications to protective equipment and changes in how the games are played. As researchers dig deeper into these connections, they are exploring novel potential treatments, including antiviral drugs, as possible preventative measures following traumatic brain injury.
The concept of “latent viruses” refers to viruses that remain present in our bodies, often for years, without causing symptoms or illness. Although the human microbiome is often associated with bacteria and other microorganisms that benefit us, it also contains a variety of viruses. Most of these viral agents do not cause immediate harm, but some can become active under specific circumstances, including stress or physical trauma. Among the most prevalent of these dormant viruses are herpes simplex virus 1 (HSV-1) and varicella-zoster virus, which are found in large percentages of the global population. Once these viruses infiltrate the brain, they can lay dormant in neurons and glial cells until triggered by various factors, such as changes in the immune system or, as recent research suggests, by physical jolts like a concussion.
Research into this phenomenon has provided critical new insights into the connection between head injuries and neurodegenerative diseases, including Alzheimer’s disease. Dana Cairns, a research associate in the Department of Biomedical Engineering at Tufts University, along with a team of researchers from Oxford University, have contributed significantly to this emerging understanding. Cairns’ earlier studies found evidence suggesting that the reactivation of HSV-1 in the brain could potentially trigger the hallmark symptoms of Alzheimer’s disease, including the buildup of amyloid plaques, neuronal loss, inflammation, and disrupted neural activity. The study raised an important question: could head trauma, akin to a concussion, serve as the physical event that “wakes up” these dormant viruses and sets the stage for the onset of neurodegenerative diseases?
The notion that viruses like HSV-1 might play a role in Alzheimer’s disease was first put forward by Ruth Itzhaki, a visiting professorial fellow at Oxford University. Over 30 years ago, Itzhaki discovered a high prevalence of HSV-1 in the brains of elderly individuals, leading her to propose that the reactivation of the virus could be involved in the development of dementia-like symptoms. Her research suggested that stress, immune suppression, and other triggers could spark viral reactivation and initiate brain damage, resulting in the cognitive decline seen in Alzheimer’s patients.
Building upon this foundation, the Tufts and Oxford team set out to test whether physical brain injury, such as a concussion, could similarly trigger the reactivation of HSV-1, resulting in neurodegeneration. To test this hypothesis, they used an innovative lab model designed to replicate the human brain’s environment. This model consisted of a 6mm-wide donut-shaped material made of silk protein and collagen, infused with neural stem cells that were cultivated into neurons. These neurons grew extensions like axons and dendrites and communicated with each other similarly to how they would in a functioning brain. The lab model was designed to mimic the process of concussion, allowing researchers to observe the effects of head injury on the brain’s tissues and see whether these forces could activate latent viruses within.
After subjecting these lab-grown tissue models to controlled jolts that simulating the effects of concussions, researchers made startling observations. When the brain tissue models were infected with HSV-1, the physical disruption resulted in the reactivation of the virus. Within hours, the hallmark symptoms of neurodegeneration emerged—amyloid plaques formed, p-tau proteins gathered in “tangles” inside neurons, glial cells proliferated in response to inflammation, and dying neurons began to accumulate. These observations mirrored the symptoms seen in Alzheimer’s disease. Furthermore, after repeated simulated concussions, the level of viral reactivation and associated brain damage worsened, demonstrating that repeated trauma could compound the negative effects and intensify the risk of neurodegeneration.
In contrast, the tissue models that were not infected with HSV-1 did experience some glial cell activation, which is a typical response to brain injury. However, they did not exhibit the damaging hallmarks of Alzheimer’s disease, suggesting that viral reactivation may be a crucial factor linking concussions to the development of long-term brain damage.
The implications of this study extend far beyond the world of sports. Each year, approximately 69 million individuals worldwide suffer from some form of traumatic brain injury (TBI), ranging from mild concussions to severe brain trauma. TBI is a leading cause of disability and death, and it is estimated that it costs the global economy over $400 billion annually. While many people associate traumatic brain injuries with athletes or people involved in violent accidents, the long-term effects of even mild concussions are a major concern for public health worldwide. The findings of this study add further weight to concerns about the potential consequences of TBI and underscore the need for preventative strategies to address the problem.
The results of Cairns’ study may pave the way for new approaches to reducing the risk of neurodegenerative diseases in individuals who suffer from brain injuries. In particular, the researchers raised the possibility that antiviral drugs or anti-inflammatory agents could be effective in preventing the reactivation of viruses like HSV-1 following concussive events. Early administration of these treatments might serve as a preventive measure, lowering the chances of developing Alzheimer’s or other neurodegenerative diseases months or even years after the injury has occurred. This concept is still in its early stages, but it highlights the potential for medications that target virus activation and neuroinflammation to stop brain damage before it can progress.
With further exploration and understanding, it may become possible to establish protocols for head injury management that go beyond physical rehabilitation and include antiviral and anti-inflammatory treatments. Such interventions could change the way clinicians approach concussion-related injuries and help reduce the long-term risks associated with head trauma.
The development of this brain tissue model also represents a significant advancement in scientific research, providing a new tool to study how trauma, infection, and neurodegeneration interact. This model has the potential to generate critical insights into the processes that underlie Alzheimer’s disease and other cognitive disorders, providing a more mechanistic understanding of the conditions. It will also serve as a valuable platform for testing new treatments, enabling researchers to screen potential drugs or therapies more efficiently and comprehensively.
The findings from this study offer a sobering look at the long-term effects of brain injuries, but they also provide hope that targeted interventions might be developed to address this pressing public health issue. While the connection between concussion, virus reactivation, and neurodegeneration is still a relatively new area of research, the possibility of early preventive treatments could reshape our approach to protecting the brain from damage, both in the realm of sports and beyond. By continuing to explore the intricate links between head injury, infection, and brain degeneration, scientists may ultimately offer new solutions for combating Alzheimer’s disease and other related conditions.
Reference: Repetitive injury induces phenotypes associated with Alzheimer’s disease by reactivating HSV-1 in a human brain tissue model, Science Signaling (2025). DOI: 10.1126/scisignal.ado6430