A serious knock to the head may also deliver an insidious blow to the human immune system – a one-two punch that could reawaken dormant viruses in the body, potentially contributing to neurodegenerative disease.
A study using stem cell ‘mini brains’ has shown that a herpes simplex virus 1 (HSV-1) infection already ‘arrested’ by the immune system can shake off its shackles when brain tissue is injured.
“We thought, what would happen if we subjected the brain tissue model to a physical disruption, something akin to a concussion?” says biomedical engineer Dana Cairns from Tufts University in the US.
“Would HSV-1 wake up and start the process of neurodegeneration?”
The answer seems to be yes. While these mini brains aren’t perfect representations of a real brain, they are good models for how brain tissue might react when experiencing repeated, mild blows to a ‘closed head’.
A week after the injury, researchers noticed the formation of clumps and tangles of proteins in the brain tissue, a hallmark of neurodegenerative diseases like Alzheimer’s.
Some of the brain cells also showed damage in line with neuroinflammation, and there were significant increases in pro-inflammatory immune cells.
Traumatic brain injuries, including chronic traumatic encephalopathy (CTE), have recently emerged as a major risk factor for neurodegenerative diseases, and preliminary research suggests chronic inflammation from even mild head trauma may play a part in the cumulative damage.
How that process plays out is not yet known, but other recent studies have found viruses may play a unique role. HSV-1 is a major risk factor for neurodegeneration, possibly doubling the chances of developing dementia.
In a 2008 study, researchers discovered the genes of HSV-1 were present in 90 percent of the protein plaques in postmortem brains of Alzheimer’s patients. The majority of this viral DNA was found within the plaques.
To further investigate whether brain injury can reactivate an HSV-1 infection, researchers at Tufts University and Oxford University turned to isolated brain slices. In response to physical injury, those infected with latent HSV-1 secreted significantly less of the excitatory neurotransmitter, glutamate.
Mini brains that were aged for 8 weeks fared better after injury than those aged for 4 weeks, indicating that head trauma may have more profound effects on young developing brains.
“Our results show that TBI causes reactivation of latent HSV-1 in our 3D brain model… and that if the injury is repeated, the damage is much greater than after a single blow,” the team concludes.
Whether HSV-1 is awoken by physical damage or another pathogen, Cairns and her colleagues suspect this super common virus is a contributing factor in the development of dementia.
They argue future studies should “investigate possible ways of mitigating or stopping the damage caused by head injury, such as anti-inflammatory and antiviral treatment after injury, thereby preventing HSV-1 reactivation in the brain and reducing subsequent development of Alzheimer’s disease.”
The study was published in Science Signaling.
