Summary: New research suggests that monotonous head trauma and concussions may restore latent viruses like HSV-1 in the brain, probably triggering degenerative diseases like Alzheimer’s. Using a mental tissue type, scientists observed that head trauma caused hidden HSV-1 to arouse, leading to mark Alzheimer’s markers such as amyloid plaques, inflammation, and cerebral damage.
These effects were only moderately damaged by repeated blows, while tissues without the disease showed minimal damage. These findings lead to the development of antimicrobial and anti-inflammatory therapies as first treatments to lessen neurodegeneration’s long-term risks from head injuries.
Important Information:
- Dormant Viruses Reactivated: Head trauma can awaken dormant infections like HSV-1, linked to Alzheimer’s signs.
- Neurodegeneration Markers: Sick head models showed amyloid plaques, swelling, and cerebral death.
- Possible Interventions: Antimicrobial or anti-inflammatory remedies may prevent virus reactivation post-injury.
Origin: Tufts University
Concussions and repeated brain trauma in sports like football and boxing are now recognized as major health threats after being once accepted as unpleasant outcomes of extreme sport competition.
Of special concern is the relationship between brain injuries and degenerative diseases such as chronic traumatic encephalopathy, Alzheimer’s disease, and Parkinson’s disease, prompting sports governing bodies to change protective equipment and rules of play to reduce the risk.
Researchers at Tufts University and Oxford University have now found connections between trauma events and the development of disease. They suggest that latent viruses that may be activated by the jolt may be causing inflammation and accumulating damage that can occur over the ensuing months and years.
The outcomes suggest that antiviral medications can be used as early preventive measures for head injuries. The findings are published in a study in , Science Signaling.
The microbiome—which includes many hundreds of bacterial species that inhabit our bodies—provides aid in digestion, immune system development, and protection against harmful pathogens. However, there are also dozens of viruses that can swarm within our bodies at any given time.
Some of these have potential to be harmful, but they simply rot in our cells. Herpes simplex virus 1 ( HSV-1 ), found in over 80 % of people, and varicella-zoster virus, found in 95 % of people, are known to make their way into the brain and sleep within our neurons and glial cells.
Dana Cairns, research associate in the Department of Biomedical Engineering at Tufts University and lead author of the study, had found evidence in , earlier studies , suggesting that activation of HSV-1 from its dormant state triggers the signature symptoms of Alzheimer’s disease in lab models of brain tissue—amyloid plaques, neuronal loss, inflammations, and diminished neural network functionality.
” In that study, another virus—varicella—created the inflammatory conditions that activated HSV-1″, said Cairns.
” We thought, what would happen if we subjected the brain tissue model to a physical disruption, something akin to a concussion? Would HSV-1 wake up and start the process of neurodegeneration”?
The link between HSV-1 and Alzheimer’s disease was first suggested by co-author Ruth Itzhaki, Visiting Professorial Fellow at Oxford University, who over 30 years ago identified the virus in a high proportion of brains from the elderly population.
Her subsequent research suggested that events like stress or immunosuppression can cause the virus to be reactivated in the brain, ultimately causing neuronal damage.
The researchers ‘ current study used a lab model to reconstruct the brain’s environment to better understand how concussions can trigger the first stages of neurodegeneration and virus reactivation.
A 6mm wide, donut-shaped sponge-like material made of silk protein and collagen is used to infect neural stem cells, grow axons and dendrite extensions, and form a network. Additionally, the stem cells can produce glial cells to help mold the brain environment and nurture the neurons.
Similar to how neurons would communicate in a brain, neurons communicate with one another through their extensions. And just like cells in the brain, they can carry within them the DNA of dormant HSV-1 virus.  ,
After placing the brain-like tissue in a cylinder and causing a sudden jolt, mimicking a concussion, Cairns went over the tissue with a microscope over time. Some of the tissue models had neurons with HSV-1, and some were virus-free.
After the controlled blows, she observed that the infected cells showed re-activation of the virus, and shortly after that the signature markers of Alzheimer’s disease, including amyloid plaques, p-tau ( a protein that creates fiber-like “tangles” in the brain ), inflammation, dying neurons, and a proliferation of glial cells called gliosis.
The same reactions, which were even more severe, were caused by additional hits with the pistons on the tissue models that mimicked repetitive head injuries. Meanwhile, the cells without HSV-1 showed some gliosis, but none of the other markers of Alzheimer’s disease.
The outcomes demonstrated that concussion-related athletes may be reactivating latent brain infections that could cause Alzheimer’s disease.
Multiple blows to the head can increase or even double the chances of developing a neurodegenerative condition months or years down the line, according to epidemiological studies.
This raises the question of whether antiviral medications or anti-inflammatory medications can be used as early preventative measures for Alzheimer’s disease in the wake of head trauma, preventing HSV-1 activation in its tracks and lowering the risk of Alzheimer’s disease, Cairns said.
The issue extends far beyond the concerns of athletes. Traumatic brain injury is one of the most common causes of disability and death in adults, affecting about , 69 million people , worldwide each year, at an economic cost estimated at$ 400 billion annually.
” The brain tissue model takes us to another level in investigating these connections between injury, infection, and Alzheimer’s disease”, said David Kaplan, Stern Family Endowed Professor of Engineering at Tufts.
” We can re-create normal tissue environments that look like the inside of a brain, track viruses, plaques, proteins, genetic activity, inflammation and even measure the level of signaling between neurons.
There is a lot of epidemiological research on environmental and other factors contributing to the risk of Alzheimer’s. The tissue model will provide a starting point for the development of new drugs and help us put that information on a mechanistic footing.
About this TBI and Alzheimer’s disease research news
Author: Mike Silver
Source: Tufts University
Contact: Mike Silver – Tufts University
Image: The image is credited to Neuroscience News
Original Research: Closed access.
” Repetitive injury causes Alzheimer’s disease-like phenotypes via reactivation of HSV-1 in a 3D human brain tissue model” by Dana Cairns et al. Science Signaling
Abstract
Repetitive injury causes Alzheimer’s disease-like phenotypes via reactivation of HSV-1 in a 3D human brain tissue model
Infection with herpes simplex virus type 1 ( HSV-1 ) in the brains of , APOE4 , carriers increases the risk of Alzheimer’s disease ( AD ).
In a three-dimensional in vitro model of APOE4-heterozygous human brain tissue, we previously discovered that latent HSV-1 was reactivated in response to neuroinflammation brought on by exposure to other pathogens.
We speculated that brain injury might reactivate latent HSV-1 in the same way that traumatic brain injury does neuroinflammation.
In either case, we examined the effects of one or more controlled blows to our human brain model in the absence or presence of latent HSV-1 infection.
After repeated, mild controlled blows, latently infected tissues showed reactivation of HSV-1, the production and accumulation of β amyloid and phosphorylated tau ( which promotes synaptic dysfunction and neurodegeneration ), and activated gliosis, which is associated with destructive neuroinflammation.
These effects are all associated with AD, dementia, and chronic traumatic encephalopathy ( CTE), and they were also increased with more injury but were not present in mock-infected tissue.
After scratch wounding, blocking the cytokine IL-1 prevented the induction of amyloid and gliosis in latently infected monolayer cultures.
We therefore suggest that the resulting reactivation of HSV-1 in the brain may contribute to the development of AD and related diseases in some people after repeated mechanical injuries to the brain, such as from direct blows to the head or jarring movements of the head.
