Dr. Teresa Murray, associate
professor in Biomedical Engineering and the Center for Biomedical
Engineering and Rehabilitation Sciences at Louisiana Tech University, is
collaborating with former Louisiana Tech doctoral student Dr. Chelsea
Pernici and professors at the University of Arizona to help develop
solutions to traumatic brain injury.
Murray and Pernici are working with Dr. Jonathan Lifshitz and Dr.
Rachel Rowe, director and research assistant professor, respectively,
with the Translational Neurotrauma Research Program at the University of
Arizona College of Medicine – Phoenix, to develop a treatment that
could prevent memory and emotional problems in patients suffering from
axonal injury caused by traumatic brain injuries (TBIs).
The study was led by Murray and Pernici who used a new imaging
technology to show how diseases and injuries affect the brain over time
and how medicines could reduce brain damage. This novel imaging was
created in Murray’s lab. Through this technology, the group of
researchers were able to repeatedly image the same axons in the brain
before and after brain injury, providing proof of TBI-related axonal
pathology.
Using a novel combination of high-resolution imaging and a GRIN lens
implanted in the brain of mice, the team documented axonal injury and
the recovery process after a blunt injury to the brain. GRIN lenses are
microscopic glass lenses that allow scientists to focus closely on the
cells for good image quality. These lenses are smaller than Lincoln’s
nose on a U.S. penny and were adopted by a handful of biologists to
better study the brain.
Murray developed an improved GRIN lens system to see more details of
brain cells. Her team also designed 3D-printed hardware to help them
find the exact same cells for each imaging session. Her improved GRIN
lenses allowed the team to find and evaluate the same injured axons over
several weeks post injury.
“The fine communication elements of neurons — axons — are torn,
ruptured and damaged, which contributes to a multitude of clinical
symptoms,” Lifshitz said. “To date, these processes have been inferred
from fixed histological sections, clinical imaging and cells in culture.
No one has observed an axon prior to injury, the consequence of injury
and the outcome. Here, we show that axons do sustain injury and can
either recover or become truncated.”
Tracking the time in which axons become affected, the team employed a
clinically approved drug, minocycline, to reduce inflammation, which
slowed axon injury, recovered them from injury and preserved function.
The team tested the drug’s effectiveness for immediate use within 45
minutes of the incident, compared to delayed use at three days post
injury – both time points showed positive effects. The minocycline drug
treatment promoted the recovery of injured axons. With treatment, a much
larger percentage of the damaged axons healed, compared to those
without treatment.
“Most brain injuries cause damage to just a few axons,” Murray said.
“These few axons can’t be seen on MRIs and CT scans. So, most TBI
patients are sent home with the hope that they will get better over
time. However, even a few damaged axons can disrupt communication in the
brain and affect neurological function.”
“The novel fluorescence imaging method using GRIN lenses allows
researchers to study brain cells in both time and space, offering a
unique opportunity to better understand the effect of drugs on brain
structure over time,” Pernici added. “It’s exciting to see that although
axons become damaged after TBI, the injury can resolve and with this
method, we have the opportunity to better understand that timescale.”
The team plans to continue their research by pairing minocycline with
another drug to further reduce this early damage. If successful, this
treatment could lessen the chances of memory loss and emotional problems
for people suffering a TBI.
“This study provides hope that we can use minocycline effectively if
the drug can be taken early in the process and not given long-term. This
could help reduce the inflammation, and thus some of the permanent
damage caused by brain injury,” Murray said.
No drug currently on the market is clinically used to prevent axon injury. The results of their research were published in
Scientific Reports on May 8.
