A rodent model of
mild traumatic brain injury

JR., Johnson RKM., Parsley MA., Xy G-Y., Infante K., DeWitt DS., Grill RJ.,
Hulsebosch CE. Journal of Neurotrauma. 2013; ahead of print

Take Home Message:
Among rats, inflammatory markers may be detected within 3 hours of a concussion
injury and other markers of brain tissue dysfunction may be detected up to 18
days after injury.

a head injury there are numerous inflammatory consequences that persist over
time and could contribute to prolonged recovery. Unfortunately, the pathologic
changes after a concussion are still poorly understood. Therefore, the purpose
of this research was to characterize the inflammatory markers as well as brain
tissue’s integrity and function 3-6 hours and 18 days after an injury. The
authors divided the rats into two groups: 1) rats given a mild traumatic brain
injury or 2) control rats who were uninjured. The rats then recovered for 3
hours, 6 hours, or 18 days; at which point their brain tissue was evaluated. On
day 11 rats performed 10 trials of beam balance assay (rat is timed
while walking from center of balance beam to a platform) and foot fault assay (rat walks on
wire mesh and researchers count the number of times forelimb or hindlimb falls
through) to assess balance and motor coordination, respectively. Within 3 hours
of injury, there were increases in several inflammatory markers within 3
different regions of the brain on the side of the injury compared to the
non-injured side of the brain. These increases were even more pronounced at 6
hours post injury and an anti-inflammatory protein had become elevated. Rats
exposed to the mild traumatic brain injury had impaired balance and locomotor
coordination compared to control animals at day 11. There was also an increase
in specific glial inflammatory
proteins (promote scarring and have detrimental affects on neuron health),
decrease in myelin (an electrical
insulating tissue that facilitates neuron efficiency), and an increase proteins
that reflect blood-brain barrier dysfunction (tightly packed layer of capillaries
that protects the brain) that persisted for 18 days.

this study, the authors found that the injured side of the brain becomes
inflamed shortly after a head injury and over time these regions may develop
scarring, tissue damage (myelin loss), and blood-brain barrier dysfunction.
This may suggest that the brain is like other tissues in that tissue damage
after an injury is a result of a combination of the initial mechanical trauma
and the delayed secondary events. The inflammatory markers that were abundant
following the injury are involved in several inflammatory pathways that can
stimulate DNA damage, cellular machinery dysfunction, and cell death. The glial
inflammatory proteins that were abundant following the injury can result in
scaring and neurodegenerative outcomes, which could lead to prolonged recovery
and adverse outcomes later in life. Furthermore, the blood-brain barrier dysfunction
may contribute to impaired vascular function, which can leave the brain more
susceptible to further downstream inflammation. This is particular interesting
in light of a recent small study that found
repeated head impacts, without a concussion, may be related to blood brain
barrier dysfunction. In addition with blood-brain barrier impairment, myelin loss
could explain adverse balance and locomotor outcomes following a brain injury.
Myelin facilitates an efficient transmission of nerve signals and if it is damaged
then signals can be compromised, which leads to less effective muscle movement.
The authors hypothesize that if treatments could alter the secondary
inflammatory cycles then perhaps we could preserve neuronal function and
decrease long-term problems. In many ways, this is similar to our concerns
about secondary injury after a musculoskeletal injury. The question remains,
what is the most effective way to reduce the secondary injury in the brain? Do
you think these inflammatory markers could also lead to concussion biomarkers
for diagnosing concussions?

by: Jane McDevitt MS, ATC, CSCS
by: Jeffrey Driban


Perez-Polo JR Ph D, Rea HC, Unabia GC, Xu G, Parsley MO, Infante SK, Dewitt D, Grill RJ Jr, & Hulsebosch C (2013). Inflammatoroy consequences mild traumatic brain injury. Journal of Neurotrauma PMID: 23360201