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mild non-significant deficits in learning the location of a platform in a
water maze. In contrast, male mTBI rats did not differ significantly
from shams during recovery but displayed marked deficits during
spatial learning. A memory retention test conducted a week after
spatial learning revealed deficits in both male and female mTBI rats.
Conclusion:
These findings confirm the validity of this novel
model at the behavioral level and research on adverse neural outcomes
is underway; preliminary data indicate that mTBI may reduce hip-
pocampal plasticity. This research has the potential to facilitate a new
way to study mTBI and may better complement research on sports-
related concussion in humans.
Keywords: Hippocampus, mTBI, Behavior, Injury
D2-02
CLOSED-HEAD SINGLE AND REPEAT CONTROLLED
CORTICAL IMPACT IN THE ADULT RAT: EFFECTS ON
BEHAVIOR, PHYSIOLOGY, AND PATHOLOGY
Naseem Jamnia
1
, Sarah Scheinman
1
, Grace Stutzmann
2,3
, Robert
Marr
2,3
, Janice Urban
4
, Daniel Peterson
2,3
, Dorothy Kozlowski
1
1
DePaul University, Dept. Biological Sciences, Chicago, USA
2
RFUMS, Center for Stem Cell Regenerative Med, North Chicago,
USA
3
RFUMS, Dept. Neuroscience, North Chicago, USA
4
RFUMS, Dept. Physiol. & Biophysics, North Chicago, USA
Recently, cases of multiple concussions in athletes have received in-
creased attention. Compared to single concussions (sTBI), repeat
concussions (rTBI) can produce significant long-term consequences
and increased risk for neurodegenerative disease. However, mecha-
nisms underlying this difference are poorly understood. We developed
a clinically relevant closed-head injury model of concussion in the
adult rat using a Leica Controlled Cortical Impact (CCI) device. Rats
were placed in a stereotax without ear-bars, on a foam-bed base. The
head was stabilized against a Plexiglas frame to control impact while
allowing head movement. A 6.5 m/s impact was delivered onto the
head surface over the sensorimotor-cortex at a depth of 10.0 mm from
the skin. rTBI animals received three injuries, 48h apart. At 5–7 days
post-injury, rats were assessed using tests of memory (Novel Object
Recognition), forelimb coordination (foot fault) and activity/anxiety
(open field). Blood corticosterone levels were measured pre-injury
and pre-sacrifice (day 8). Results indicate that both sTBI and rTBI
animals show deficits in coordination and hypo-locomotion. sTBI rats
showed no anxiety but rTBI rats showed a trend towards less time
spent in the center of an open field. sTBI rats displayed memory
deficits 3d but not 7d post-injury while rTBI rats still showed memory
deficits at 7d. Both had higher resting corticosterone levels post-
injury. No obvious gross pathology was observed on the cortical
surface or in coronal sections. Our data presents a model of closed-
head CCI in an adult rat that results in clinically relevant markers of
concussion and a delineation between sTBI and rTBI.
Keywords: memory, concussion, motor, anxiety, repeat concussion
D2-03
A COMPUTATIONAL MODEL OF CORTICAL NETWORK
FOR QUANTIFYING NEUROBEHAVIORAL SEQUELAE OF
CONCUSSION LINKED TO TRAUMATIC AXONAL INJURY
Jianxia Cui
, Laurel Ng, Vladislav Volman
L-3 Communications/Applied Technologies, Inc., Simulation, Engineer-
ing & Testing, 10770 Wateridge Circle Suite 200, San Diego, USA
Background:
Mild traumatic brain injury (mTBI) often results in
neurobehavioral alterations such as impaired attention, increased re-
action time, and deficits in working memory. Diffusion imaging, post
mortem studies, and animal models suggest that mTBI primarily af-
fects myelinated axons in white matter tracts. We sought to quantify
the neurobehavioral manifestations of concussive mTBI that are
linked to traumatic injury of myelinated axons.
Methods:
A large-scale biophysically plausible model of cortical
tissue was created for studies of neurobehavioral manifestations of
traumatic axonal injury. The network was composed of 5120 pyra-
midal neurons and 1280 inhibitory neurons, communicating via glu-
tamatergic and GABAergic synapses. Importantly, the model
architecture reflected intra- and inter- hemispheric cortical organiza-
tion, including the distribution of non-myelinated and myelinated
(callosal) axons and axonal conduction delays. Injury was applied to
model corpus callosum axons for quantifying the resulting alterations
in cortical dynamics.
Results:
The intact model exhibited collective oscillations in the
alpha band (8–12 Hz) that are routinely observed in resting non-
attending human subjects. Callosal injury induced several clinically
observable changes, including injury dose dependent increases in: 1)
theta-to-alpha spectral power, as observed in qEEG studies, 2) re-
duced response to attention-like stimulation, and 3) increased popu-
lation response time, similar to increased reaction time as observed in
neurobehavioral tests on mTBI subjects.
Conclusions:
The model results were in a good semi-quantitative
agreement with the existing experimental data. This effort is part of a
larger goal to link a series of models together in an end-to-end
fashion to identify a neurologically based mechanism of concussion
and its implication regarding the prognosis and diagnosis of con-
cussion. Computational models of white matter biomechanical re-
sponse and neurological changes have been developed and are used
in conjunction with the present model to complete the linkage of
external loading conditions to neurological outcomes. The present
model can be used as a platform for modeling neurobehavioral se-
quelae of mTBI and for linking the observed outcomes to specific
injury scenarios.
Keywords: cortical network, neurobehavioral sequelae, reaction
time, qEEG
D2-04
VISUAL DYSFUNCTION SCREENING IN MICE AFTER TBI
USING AN OPTOMOTOR ASSESSMENT OF THE OPTOKI-
NETIC RESPONSE
Scott Ferguson
, Benoit Mouzon, Destinee Aponte, Michael Mullan,
Fiona Crawford
Roskamp Institute, Neurobehavior, Sarasota, USA
Introduction:
Our mouse model of repetitive mild TBI (r-mTBI)
produces chronic optic nerve pathology and retinal degeneration.
In order to assess the visual function of the mice, we have opti-
mized a mechanical optomotor assay to assess the optokinetic
response.
Methods:
The optomotor apparatus consisted of a rotating drum
containing black and white stripes at varying angular resolutions.
Mice were acclimated to the apparatus for a period of 5 minutes in
phototopic lighting. Optomotor testing at each resolution consisted
of pairs of 2 minute trials with 1 trial in a clockwise rotation fol-
lowed by 1 trial in a counter-clockwise rotation with an inter-trial
time of 30 seconds. Following the completion of the first pair of
trials in photopic conditions, lighting was dimmed to scotopic
A-101