Concussion Discovery Reveals Dire, Unknown Effects of Even Mild TBI
From: University of Virginia Health Care
System
- UVA
researchers have discovered that concussions and traumatic brain injuries
(TBI), even when mild, cause swelling that blocks the brain’s ability to
clean itself of harmful toxins and debris.
- In
addition to an immediate impact on memory and brain inflammation, this may
set the stage for Alzheimer’s, dementia and other neurodegenerative
diseases.
- The
discovery helps explain why repeated brain injuries are so harmful and
suggests they up the risk of long-term problems.
- It
also suggests a reason why blows to the head affect different people
differently.
- The
findings point to a new approach to treating brain injury and could lead
to a better way to determine when it is safe for athletes and military
personnel to resume their duties.
Even mild concussions cause severe and
long-lasting impairments in the brain’s ability to clean itself of toxins, and
this may seed it for Alzheimer’s disease, dementia and other neurodegenerative
problems, new research from the School of Medicine reveals.
The discovery offers important insights
into traumatic brain injury (TBI), a poorly understood condition that has
become a major public concern, particularly in sports and for the military. The
findings help explain why TBI is so harmful and why it can have such long-term
effects. The research also suggests that certain patients are at greater risk
of a decline in brain function later in life, and it paves the way for new and
better treatments.
“This provides some of the best evidence
yet that if you haven’t recovered from a brain injury and you get hit in the
head again, you’re going to have even more severe consequences,” said John
Lukens, PhD, of UVA’s Department of Neuroscience and the Center for Brain
Immunology and Glia (BIG). “This reinforces the idea that you have to give
people an opportunity to heal. And if you don’t, you’re putting yourself at a
much higher risk for long-term consequences that you might not see in a year
but could see in a couple of decades.”
New Understanding of TBI
Lukens’ research identifies a previously
unknown consequence of TBI that can have long-lasting effects. When the brain
swells, it presses against the skull; trapped in-between are tiny lymphatic
vessels that clean the brain. This pressure on the vessels, the UVA researchers
found, causes serious and long-lasting impairment of the brain’s ability to
purge itself of toxins. Working with lab mice, one of the best models of TBI
available, the scientists found the impairment could last at least two weeks –
a long time for mice – and possibly much longer.
These lymphatic vessels were identified
by Jonathan Kipnis, PhD, and his collaborators at UVA in 2015. Until then,
medical textbooks insisted the vessels did not exist and that the brain was
“immune privileged,” meaning that it did not interact with the immune system.
UVA’s discovery changed all that, and Kipnis has since determined the
vessels play important roles in both Alzheimer’s and the cognitive decline
that comes with age.
Now they emerge as an important player
in TBI. “We know that traumatic brain injury carries an increased risk for a
bunch of long-term issues like dementia, Alzheimer’s disease and CTE [chronic
traumatic encephalopathy], and this has really been made extra public because
of the NFL,” said researcher Ashley C. Bolte, an MD/PhD student. “Then there’s
also anxiety, depression, suicide. The reasons why TBI results in increased
risk for this isn’t totally known, and we think that our findings might provide
a mechanism as to why.”
People Most at Risk
The research suggests that people who
have pre-existing problems with their brain drainage, either from prior
concussions or naturally, are likely to suffer much more severe consequences
from TBI. In mice, this led to more brain inflammation and worse outcomes,
including memory impairment. “If you have a pre-existing kink in the pipes and
you get hit in the head, then everything is taken to a higher level – the
impacts on memory, the neuro-inflammation,” Lukens said. “There are a lot of
implications to it.”
Emerging imaging technology may
eventually make it possible for doctors to identify people who will suffer the
greatest consequences of TBI. More good news: Lukens also believes that doctors
may one day be able to rejuvenate the impaired lymphatic vessels with drugs to
improve patients’ outcomes and possibly stave off long-term consequences. (This
also may prove useful in the battle against the cognitive decline that
naturally occurs with age.)
In addition, Lukens said, it eventually
may be possible for doctors to evaluate brain drainage after injury to
determine when it is safest for patients to return to action.
“Right now, we really don’t know what to
tell these kids who want to get back out on the field, or even members of the
military,” Lukens said. “It would be important to have empirical tests to say
you can continue or never to do those things ever again.”
About the TBI Research
The researchers have published their
findings in the scientific journal Nature
Communications. The research team consisted of Bolte, Arun B. Dutta, Mariah
E. Hurt, Igor Smirnov, Michael A. Kovacs, Celia A. McKee, Hannah E. Ennerfelt,
Daniel Shapiro, Bao H. Nguyen, Elizabeth L. Frost, Catherine R. Lammert, Kipnis
and Lukens.
This work was supported by the National
Institutes of Health’s National Institute of Neurological Disorders and Stroke
(grant R01NS 106383), the Alzheimer’s
Association (grant AARG-18-566113), the Owens Family Foundation and a
University of Virginia Research and Development Award. Bolte and Kovacs were
supported by a Medical Scientist Training Program Grant (5T32GM007267-38) and
an Immunology Training Grant (5T32AI007496-25). Lammert was supported by an NIH
National Institute of General Medical Sciences pre-doctoral training grant
(3T32GM008328) and a Wagner Fellowship. Frost was supported by a National
Multiple Sclerosis Foundation Postdoctoral Fellowship (FG-1707-28590).
No comments:
Post a Comment