135 / 198
1
John D. Dingell VA Medical Center; Wayne State University, Neu-
rosurgery, Detroit, USA
2
Wayne State University, Psychiatry and Behavioral Neurosciences,
Detroit, USA
3
Wayne State University, Anesthesiology, Detroi, USA
Individuals with mild traumatic brain injury (mTBI) often develop
affective changes such as anxiety, depression, or symptoms resem-
bling posttraumatic stress disorder (PTSD). It is not clear how mTBI
induces PTSD-like symptoms, although studies show activation
changes in brain regions involved in fear learning; such as prefrontal
cortex (PFC), amygdala (AMY), and hippocampus (HC); with dorsal
(dHC) and ventral (vHC) demonstrating subregion-specific responses.
Here, we used a mouse model of mTBI to examine effects of injury on
fear behaviors and associated neurochemical alterations.
Anesthetized male C57BL/6 mice (10–12 wk) given a mild, midline
impact over intact skull, sham surgery, or no surgery (naı¨ve) were
assessed for fear response (freezing) to contextual fear conditioning
(FC) at 14 d post-injury, using a 5-phase paradigm (habituation, ac-
quisition, extinction, reinstatement, reinstatement recall). Brains were
harvested for proton magnetic resonance spectroscopy (
1
H-MRS)
analysis
ex vivo
at 25 d post-injury for excitatory/inhibitory neuro-
chemical assessment.
mTBI mice demonstrated increased freezing during acquisition and
extinction, compared to controls (combined naı¨ve/sham). No differ-
ences in freezing emerged between groups at baseline or reinstate-
ment; but mTBI mice showed more freezing during reinstatement
recall, compared to controls. At 25 d post-injury, HC exhibited sub-
region-specific neurochemical profiles: decreased dHC GABA and
increased vHC glutamate in mTBI compared to controls. PFC and
AMYG did not differ neurochemically between mTBI and controls.
Changes observed in conditioned fear in mTBI mice resemble FC
reported in PTSD and observed clinically in mTBI. Decreased dHC
GABA may reflect reduced inhibitory neurotransmission, with in-
creased vHC glutamate reflecting greater excitatory neurotransmis-
sion. These data suggest increased excitatory tone in both regions,
achieved through different mechanisms. This model of mTBI-induced
alterations in FC may give insight into regionally distinct HC influ-
ence on the development of affective disorders following mTBI.
Keywords: Mild TBI, Fear Conditioning, Magnetic Resonance
Spectroscopy, GABA/Glutamate, Mouse Model, Hippocampus
D1 Poster Session VII - Group D: Bioengineering
D1-01
SUBCONCUSSIVE HEAD IMPACT HISTORY FOR CON-
CUSSED AND NON-CONCUSSED COLLEGE FOOTBALL
PLAYERS
Brian Stemper
, James Murtha, Alok Shah, Daniel Sjoquist, John
Humm, Ashley LaRoche, Adam Pfaller, Michael McCrea
Medical College of Wisconsin, Neurosurgery, Milwaukee, USA
Head impact history has become a significant clinical factor for
concussion, with studies reporting more problematic outcomes for
athletes that sustained 3
+
concussions. Experimental studies report
decreased biomechanical tolerance for animals that sustained prior
concussions. It can be hypothesized that subconcussive head impact
history influences concussion risk in humans. The current objective
was to outline differences in subconcussive impact history between
concussed and non-concussed athletes. Division III college football
players were consented and enrolled for the 2013 season. Head impact
metrics were collected for games and contact practices using xPatch
acceleration sensors (X2 Biosystems, Seattle, WA). Impact data were
collected for 185 non-concussed and 11 concussed players. Data were
divided between 4 position groups (number concussed): offensive line
(1), offensive backs (3), defensive line (4), and defensive backs (3).
Concussive impacts had a median linear acceleration of 77 g. The
number of subconcussive impacts above 25% of the median concus-
sive acceleration was compared between concussed and non-
concussed groups. Analysis was divided between games and practices
and normalized by number of games/practices per player. For con-
cussed players, impacts before the injury dates were analyzed.
Overall, 35% more subconcussive impacts were sustained during
games than practices. Concussed defensive players had 103% more
subconcussive impacts than non-concussed defensive players during
games (
+
133% for backs,
+
73% for linemen). This trend was not
evident for defensive players during practices or offensive players
during games or practices. Although the trend for pre-injury sub-
concussive exposure for concussed defensive players is intriguing,
these data in general do not support the hypothesis that subconcussive
head impact history contributes to greater concussion risk. However,
this study included a limited dataset and significant trends may
emerge with larger sample sizes. Nonetheless, this forms the basis for
ongoing investigation into effects of subconcussive impact history on
risk and biomechanics of athlete concussion.
Keywords: head acceleration, traumatic brain injury, biomechanics
D1-02
SEX-BASED BEHAVIORAL DIFFERENCES IN RATS FOL-
LOWING HEAD ROTATIONAL ACCELERATION INJURY
Brian Stemper
1,3
, Alok Shah
1,3
, Rachel Chiariello
1,3
, Natasha
Wilkins
1,3
, Christopher Olsen
2
, Matthew Budde
1,3
, Frank Pintar
1,3
1
Medical College of Wisconsin, Neurosurgery, Milwaukee, USA
2
Medical College of Wisconsin, Pharmacology & Toxicology, Mil-
waukee, USA
3
Zablocki VA Medical Center, Research Service, Milwaukee, USA
Literature-supported evidence highlights sex-based differences in
traumatic brain injury (TBI) outcomes (clinical and pathological)
between males and females. Animal models can quantify these dif-
ferences in a controlled laboratory environment using identical injury
exposures and assessments focused on specific outcomes. This study
exposed anesthetized male and female Sprague-Dawley rats to head
rotational acceleration or sham procedure. Acceleration magnitude and
duration were identical between male and female rats (363 krad/s
2
,
3.4 msec). Control rats were exposed to a sham procedure that was
identical to the injury protocol without head rotational acceleration.
Behavioral assessments conducted during the first week following
injury included Morris Water Maze (MWM) and Elevated Plus Maze
(EPM). Unconsciousness time immediately following injury was not
significantly different, although male rats had 22% shorter uncon-
sciousness times. Female rats demonstrated greater post-injury ac-
tivity, with significantly increased number of EPM arm changes
(p
<
0.05) for injured female rats compared to injured male rats.
Compared to sex-matched controls, injured females had 113% in-
creased whereas males had only 20% increased number of arm
changes. Male rats demonstrated altered emotionality following in-
jury, with 25% more time in the EPM open areas per entry compared
to controls. Injured female rats spent the same amount of time in
the open areas of the EPM per entry as controls. Compared to sex-
matched controls, injured male rats demonstrated significantly in-
creased MWM unsuccessful trials (p
<
0.05,
+
142%), along with
greater latency to find the hidden platform during the first (
+
28%) and
A-99