Tracey Romero • Wed, March 1st, 2017
A new concussion model of repeat, mild, bilateral traumatic brain injury
(TBI) induced earlier onset of familial amyotrophic lateral sclerosis
(ALS) symptoms in rats with the human SOD1 mutation (SOD1), providing
a better understanding of the relationship between TBI and neurodegenerative diseases.
The model developed by Gretchen Thomsen, Ph.D., of the Regenerative Medicine
Institute at Cedars-Sinai Medical Center in Los Angeles and colleagues,
was published in the December 2016 issue of the Journal of Trauma and
Acute Care Surgery.
Thomsen recently shared her research during a sports concussion panel
at a Cedars-Sinai conference, “Regenerative and Neurological Trauma:
From the Playing Field to the Battlefield,” held February 9 and
10, 2017 at Sofitel Los Angeles at Beverly Hills in Los Angeles, California.
The conference featured two days of scientific sessions on military sports
concussions/traumatic brain injury, spinal cord trauma, and regenerative
Traumatic Brain Injury and Neurodegenerative Diseases
Thomsen and her colleagues have been using animal models to look at amyotrophic
lateral sclerosis (ALS) and long term effects of brain injury. She explained
that while they see the phenomenon of chronic traumatic encephalopathy
(CTE) and ALS in athletes, the mechanisms by which this may happen and
how it relates to type of impact hasn’t been clear.
To develop their most recent model, Thomsen and colleagues evaluated functional
and pathological consequences of repeated traumatic brain injury (TBI)
over time in wild type rats and rats harboring the human SOD1 (“SOD1”)
mutation, a model of familial amyotrophic lateral sclerosis (ALS). The
rats at 60 days of age were exposed to mild, bilateral TBI once per week
for either two weeks or five weeks using a controlled cortical impact
device. The two-week injured rats initially recovered motor function,
but never recovered to baseline during the 12-week study. The five-week
injured rats exhibited more significant deficits overall. The SOD1 TBI
rate also showed early onset of the ALS phenotype.
Thomsen and colleagues concluded, “Unlike previous models of repeat
brain injury, which demonstrates only transient deficits in motor function,
our concussion model of repeat, mild, bilateral TBI induced long-lasting
deficits in motor function, decreased cortical thickness, shrinkage of
the corpus callosum, increased brain tauopathy, and earlier onset of ALS
symptoms in SOD1 rats.
“This model may allow for a greater understanding of the complex
relationship between TBI and neurodegenerative diseases and provides a
potential method for testing novel therapeutic strategies.”
Thomsen told OTW, “We now have a good model of CTE. Before we thought
mice could recover from mild impact, but now we know that when there is
repeat impact, the brain can’t recover.”
She also said they are looking at biomarkers and imaging studies in these
animal models to help understand repetitive brain injury in humans and
to develop therapeutics for treatment. The hope is that by developing
these animal models, they won’t have to wait until an athlete dies
to understand the impact the concussion has on the brain. They also hope
to create variations of the models to relate to different populations
like soccer and football.
Collaboration Between Scientists, Clinicians and Athletes
Besides new research, collaboration between scientists, clinicians and
athletes was also a focus of the conference. Two former professional athletes,
Ex-NFL football player Ben Utecht, author of Counting the Days While My
Mind Slips Away: A Love Letter to My Family; and ex-Major League Soccer
player Alecko Eskandarian, now assistant coach for the New York Cosmos,
also participated in the concussion panel with Thomsen, sharing their
personal experiences with concussion-related brain damage.
“It was really important to have these retired athletes be a part
of the conversation and have dialogue with the scientists and clinicians,”
Thomsen said. She is a soccer player herself, having played division one
at Villanova University and later in W-League. “I used to head the
ball for an hour after practice and now I look back and ask will I let
my child do this?” Because there are also so many nonprofessional
athletes, she believes that they should be a part of the conversation
Eric Ley, M.D., director of the Surgical Intensive Care Unit and director
of the Surgical Care Fellowship Program at Cedars-Sinai and Vernon B.
Williams, M.D., a physician with Kerlan-Jobe who specializes in pain management
and sports neurology also participated in the conference, which was co-sponsored
by the Cedars-Sinai Board of Governors Regenerative Medicine Institute,
the Cedars-Sinai Department of Surgery and the Kerlan-Jobe Orthopaedic
Clinic, a Cedars-Sinai affiliate.
Williams’ presentation was on “Clinical evaluation of sports
concussion: what we know…and wish we knew,” and one of the
topics he discussed was the guidelines on sports concussions. He explained
that most guidelines talk about the signs and symptoms of concussion and
risk factors and tools for evaluation, adding that most experts agree
with the guidelines whether they are evidence-based or from a consensus
“This information is necessary if you are managing athletes, but
there is so much more we really should know,” Williams said. “We
are all interested in a collaboration between scientists and clinicians.
Part of the goal of interaction is to help one another,” he said.
He explained that clinicians could share what questions they have about
brain injury with scientists to help guide research, and scientists can
in turn share with clinicians what they are finding out in the lab.
He added, “We wish we knew why some people will recover quickly,
while others have lingering symptoms. When a patient comes in with a concussion,
it is hard to tell where he or she will fall.”
He also wished there was a better understanding of genetic and environmental
factors. For example, he explained that we have non-neurological contributors
like depression that can’t be studied in a lab.