Page 75 - NNS 2014 Program & Abstract Book

disease (AD) pathological and cognitive changes. Notwithstanding the
limitations inherent in retrospective studies, the evidence suggests that
head injury is an important risk factor for the subsequent development
of dementia. We hypothesized that a single closed head injury would
accelerate the onset of cognitive impairment in a mouse model of AD.
APP/PS1 KI (AD) mice and their wild-type (WT) littermates received
a closed head injury (CHI) at 8 months of age, prior to cognitive
deficits in the AD mice. Cognitive changes were measured at 1 mo
post injury by radial arm water maze (RAWM). CHI AD mice were
found to have a significant impairment in RAWM compared to sham
AD mice and CHI WT mice. Currently, little is known about how a
single head injury accelerates onset of AD; yet, clinically, neuroin-
flammation has been found to be chronically elevated after a single
head injury suggesting a failure to resolve the healing process. As
neuroinflammation can affect AD neuropathology and cognitive im-
pairment, we tested whether an altered inflammatory response fol-
lowing a traumatic brain injury might be a contributing factor.
Temporal changes in amyloid and glial responses were measured at
9 h, 24 h, 7 d, and 2 mo post injury. Unexpectedly we found in the
injured AD mice that the temporal astrocyte and cytokine/chemokine
response was delayed compared to injured WT mice. However, once
activated, the glial injury response (cytokine/chemokines and micro-
glia/astrocyte markers) in the AD mice failed to resolve compared to
the WT injured mice. In agreement with clinical findings, our ex-
perimental model suggests that a single head injury can accelerate
cognitive impairment, and that the mechanism may involve an unre-
solved neuroinflammatory response in injured AD mice. Future
studies are ongoing to test this possibility.
Key words
Alzheimer’s disease, astrocyte, closed head injury, cytokine, micro-
glia, radial arm water maze
A5-02
BLAST EXPOSURE IMPAIRS THE BRAIN’S ABILITY TO
MODULATE SENSITIVITY TO SENSORY INFORMATION:
EVIDENCE FROM THE VETERAN POPULATION
Papesh, M.A.1, Gallun, F.1,2, Leek, M.1,2, Billings, C.J.1,2, Folmer,
R.1,2, Storzbach, D.1,2
1OHSU, Portland, OR
2Portland VAMC, Portland, OR
Based upon the constellation of chronic multisensory and cognitive
problems frequently exhibited by Veterans exposed to high-intensity
blast waves, we hypothesized that blast exposure may damage the
neural networks involved in filtering sensory information.
We assessed the auditory filtering characteristics of a group of
blast-exposed Veterans and non-blast-exposed control participants
using self-report, behavioral, and electrophysiological measures. Self-
report indices included the Neurobehavioral Symptom Inventory
(NSI), the Sensory Gating Inventory (SGI), and the Functional
Hearing Questionnaire (FHQ). Behavioral measures included speech
comprehension, the Comprehensive Trail Making Test (CTMT), and
the Stroop Color-and-Word test. Objective measures of auditory fil-
tering included the auditory P300 oddball paradigm, the sensory
gating paradigm, the intensity dependence of auditory evoked po-
tentials (IDAEP), and habituation and prepulse inhibition of the
acoustic startle response (ASR).
Preliminary results indicate that blast-exposed Veterans have higher
rates of perceived sensory and cognitive dysfunction compared to
control participants as revealed by significantly higher scores on the
NBSI, SGI, and FHQ. Stroop testing revealed that blast-exposed
Veterans were slower to respond on all portions of the test. Blast-
exposed Veterans also scored below average on portions of the CTMT
requiring attention to specific visual stimuli while ignoring visual dis-
tractors. Electrophysiological test measures demonstrated poor habitu-
ation to ASR stimuli, reduced sensory gating measured at both pre- and
post-attention levels of processing, and markedly reduced responses to
the auditory P300 oddball stimulus compared to control participants.
Poor habituation to ASR stimuli, reduced sensory gating, and below
average scores on the CTMT all indicate an inability to inhibit re-
sponses to irrelevant stimuli in blast-exposed Veterans, while reduced
P300 responses reveal reduced capacity for neural response to novel
or rare stimuli. Overall, these results indicate that blast exposure re-
duces one’s ability to appropriately respond to novel stimuli while
ignoring distracting stimuli, a condition which likely contributes to
downstream cognitive issues.
Key words
auditory, blast exposure, sensory processing, traumatic brain injury,
veterans
A5-03
APPLICATION OF AN ACTIVE AVOIDANCE TASK IN DE-
TECTING COGNITIVE DEFICITS FOLLOWING PENE-
TRATING BALLISTIC-LIKE BRAIN INJURY
Chen, Z.Y., Lu, X.M., Liao, Z.L., Tortella, F., Shear, D.
Walter Reed Army Institute of Research, Silver Spring, MD
In this study we used a modified active avoidance (AA) task to
characterize cognitive deficits associated with emotional distress in
rats following penetrating ballistic-like brain injury (PBBI). The AA
device consists of a revolving arena covered by shock pads that are
electrically charged only when rotating into a designated shock zone
(SZ) (1/6 of the arena area). The goal of AA is for animals to learn to
use environmental cues to avoid entering the SZ. Anaesthetized rats
received PBBI (5% or 10% injury severity) or sham surgery. At 7 days
post-injury (DPI), each rat was habituated to the arena (10-min) with
the SZ turned off. On post-injury days 8 and 9, the rats received two
avoidance acquisition trials per day (5 min/trial; 1 h ITI) in the re-
volving arena with the SZ turned on. At 10 DPI, the SZ was shifted
180 and the animals were exposed to a reversal learning test (4 trials;
5 min/trial; 1 h ITI). No significant injury-induced alterations in
spontaneous locomotor behavior were detected during the habituation
trial. However, results of AA acquisition trials and reversal tasks re-
vealed significant injury-severity dependent deficits. More specifi-
cally, compared to sham controls, PBBI animals made more entries
into the SZ (Sham: 1.9 – 1.1; 5% PBBI: 3.5 – 2.1; 10% PBBI:
9.9 – 2.9) and displayed significantly longer escape latencies (Sham:
2.1 – 1.5s; 5% PBBI 10.9 – 8.7s, 10% PBBI: 22.9– 8.8s) on the last
day of acquisition. Similar deficits associated with injury severity
were also detected on the reversal test for entry frequency: (Sham:
2.0 – 0.8; 5% PBBI: 7.0 – 3.1; 10% PBBI: 10.8 – 3.6), and escape la-
tency (Sham: 20.6 – 6.8s; 5% PBBI: 31.8 – 6.9s; 10% PBBI: 42.0 –
12.6s). Overall, these results indicate that the AA task provides a
sensitive measure for detecting cognitive dysfunction in the PBBI
model. While ongoing work will determine whether this task would be
sensitive to mild TBI, the current results suggest this may provide a
useful measure for detecting efficacy of promising pharmacother-
apeutics in the PBBI model.
Key words
active avoidance task, learning and memory, penetrating ballistic-like
brain injury
A-43