Top Student Competition Finalists
T1-01
REPEAT MILD TRAUMATIC BRAIN INJURY IN ADO-
LESCENT RATS ACCELERATES ALZHEIMER’S DISEASE
PATHOGENESIS
Grant, D.A.
, Teng, E., Serpa, R.O., Prins, M.L.
University of California, Los Angeles, Los Angeles, USA
Traumatic brain injury (TBI) is a risk factor for Alzheimer’s disease
(AD), but the cumulative effects of mild repeat TBI (RTBI) in the ad-
olescent brain on AD pathogenesis are unknown. We hypothesized that
RTBI would increase secretase concentration acutely in the wild-type
Sprague-Dawley rats and accelerate the accumulation of amyloid beta
(A
b
) chronically in amyloid precursor protein/presenilin 1 transgenic rats
(APP/PS1). Postnatal day 35 (P35) male wild-type rats received sham or
4 RTBI at 24 hour intervals (4RTBI
24
) using a closed-head injury model.
Bilateral cortices were analyzed 24 or 48 hours post-injury using western
blots to measure the concentration of beta-site-APP-cleaving-enzyme-1
(BACE1) and PS1, two secretases required for A
b
production. The P35
APP/PS1 rats received sham, 4RTBI
24
or 4 RTBI at 72 hour intervals
(4RTBI
72
) and were perfused at 12 months of age. One-way ANOVA
with Tukey-Kramer post-hoc was used to compare optical densities of
BACE1, PS1, and total A
b
deposits (including puncta, clusters, and
plaques) between injury groups. In wild-types, 4RTBI
24
increased 24
hour BACE1 levels in ipsilateral cortex 35% greater than sham
(p
=
0.02), but returned to sham levels by 48 hours. 4RTBI
24
did not
affect PS1 levels in wild-type rats at either time point. In APP/PS1 rats,
4RTBI
24
had significantly more A
b
deposits in the ipsilateral hippo-
campus relative to the sham (p
=
0.040) and 4RTBI4
72
(p
=
0.046) groups,
which did not differ from each other. There was no difference between
ipsilateral and contralateral hippocampi. These findings demonstrate that
repeat injuries in adolescence may accelerate subsequent A
b
deposition.
Since BACE1 increased transiently, its relationship with chronic A
b
remains uncertain. Interestingly, when injury levels were increased to
allow metabolic recovery between impacts, chronic A
b
deposition is
similar to that seen after sham. This study emphasizes the need for
compliance in return-to-play guidelines to minimize the risk for accel-
erated A
b
accumulation among those pre-disposed to AD.
Supported by UCLA BIRC, KO8AG34628, NS058489-01
Key words
Alzheimer’s disease, developmental, mild TBI
T1-02
THE DEVELOPMENT OF EPILEPTOGENIC ACTIVITY
AFTER DIFFUSE BRAIN INJURY IN SWINE
Ulyanova, A.V.
, Koch, P.F., Grovola, M.R., Harris, J.P., Cullen,
D.K., Wolf, J.A.
University of Pennsylvania, Department of Neurosurgery, Philadel-
phia, USA
The potential mechanisms of epileptogenesis after diffuse brain injury
were studied using a model of closed-head rotational acceleration in
swine. We performed in vivo extracellular recordings in order to in-
vestigate changes in hippocampal function post injury. We compared
baseline oscillatory activity and responses to stimulation in sham,
single, and repetitively injured animals.
Male Yucatan swine (6m) underwent coronal rotational accelera-
tion (180–260 rad/sec) with little or no loss of consciousness and
minimal subdural bleeding. We recorded changes in the synaptic in-
puts post stimulation with 32-channel probes and correlated the results
to our previous in vitro hippocampal slice recordings 7 days post
injury. Paired-pulse paradigms were utilized in order to examine
changes in excitability and neurotransmitter release, while theta burst
stimulation was induced to provoke epileptiform activity.
Hippocampal recordings were analyzed for epileptiform activity,
synaptic facilitation, and changes in excitability after theta burst
stimulation. Stimulation was performed in the Schaffer collaterals and
the entorhinal cortex while recording from all layers of the dorsal
hippocampus. Traces recorded in CA1 in response to single and paired
stimulations had significantly altered waveforms. Paired pulse facili-
tation in CA1 was altered at 7 d post injury, potentially due to changes
in neurotransmitter release probability. There were also significant
changes in responses to single pulse stimulation after theta burst
stimulation, as well as altered baseline activity (sharp waves and
paroxysmal depolarizing shifts) compared to sham. Responses to
stimulation in animal injured twice (2X180 rad/sec, 7 days apart)
produced long-lasting depolarization compared to a single injury.
These alterations suggest an increased post-synaptic excitability or a
shift in the excitation-inhibition balance of the local circuitry.
These data suggest that diffuse brain injury may induce hippo-
campal axonal and synaptic dysfunction, and changes in hippocampal
cellular excitability. Over time post injury these changes may lead to
circuit-level changes in the hippocampus that will elicit sub-clinical
epileptiform activity and potentially lower seizure thresholds.
Support: CURE Taking Flight, VA RRD Merit
Key words
circuitry, electrophysiology, excitability, hippocampus, in vivo, mild
traumatic brain injury (mTBI)
T1-03
AUDITORY SELECTIVE ATTENTION IMPAIRMENTS IN
BLAST-EXPOSED VETERANS WITH TRAUMATIC BRAIN
INJURY
Bressler, S.C.
1
, Bharadwaj, H.
1
, Choi, I.
1
, Bogdanova, Y.
2
, Shinn-
Cunningham, B.G.
1
1
Boston University, CompNet, Boston, MA, USA
2
VA Healthcare Boston, Jamaica Plain, MA, USA
A common complaint among returning combat veterans who have
experienced some form of blast-related traumatic brain injury (bTBI)
A-2
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