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to hypobaria equal to 8000 ft for 6 hr, starting at 6, 24, 72 hr or 6 days
post-blast. At 7 days post-blast, rats were perfusion-fixed and their
brains analyzed for evidence of axonal fiber injury and cerebrovascular
injury. Other rats were used for neurobehavioral assays at 14 days. The
number of de Olmos silver-stained axonal fibers present in the internal
capsule was two-times greater in animals (10/group) exposed to 100 G
blast than in shams. Animals exposed to 6 hr hypobaria at 6, 24, 72 hr
and 6 days after blast all exhibited significantly more silver-stained
fibers than those not exposed to hypobaria. Rats exposed to 100% O
2
during hypobaria at 24 hr post-blast displayed significantly greater silver
staining than those exposed to 21% O
2
(room air) during hypobaria. The
cortical area occupied by von Willebrand Factor (vWF) immunoreac-
tivity was very low in shams and over ten-times greater in blast/nor-
mobaric animals or blast/hypobaric animals. Quantitative rtPCR
indicated a 10-fold increase in vWF gene expression at 7 days post-
blast. The number of foot-faults observed during the balance beam test
was significantly greater in blast/hypobaric (100% O
2
) animals com-
pared to shams, or blast/hypobaric (21% O
2
) animals. We conclude that
AE-relevant hypobaria worsens brain injury in rats cause by blast-in-
duced acceleration and that this injury is further exacerbated by expo-
sure to 100% O
2
during hypobaria. Supported by US Air Force
FA8650-11-2-6D04 and US Dept. of Defense W81-xWH-13-1-0016
Keywords: blast, axonopathy, hypobaria, vasculopathy
C2-05
DIFFUSE TRAUMATIC BRAIN INJURY RESULTS IN BI-
MODAL VARIATION OF SYNAPTIC MARKER EXPRESSION
IN THE SOMATOSENSORY CORTEX OVER TIME
Hazel May
1–3
, Sarah Ogle
5,2,3
, Rachel Rowe
2–4
, Aida Khodadad
2,3
, P.
David Adelson
2,3
, Jonathan Lifshitz
2–4
, Theresa Thomas
2–4
1
University of Bath, Department of Biology and Biochemistry, Bath,
UK
2
University of Arizona, Child Health, Phoenix, USA
3
BARROW Neurological Institute at Phoenix Children’s Hospital,
Child Health, Phoenix, USA
4
Phoenix VA Healthcare System, Research service, Phoenix, USA
5
Banner University Medical Center, Surgery, Phoenix, USA
Diffuse traumatic brain injury (dTBI) induces multifocal axonal pa-
thology and deafferentation, which subsequently leads to axonal regen-
eration. Over time this regeneration may result in adaptive and
maladaptive circuit reorganization, with synaptogenesis being integral to
the reorganization process. The time course for synaptogenesis is not well
understood. In rodents, dTBI results in late-onset sensory-sensitivity
(neurological impairment) to whisker stimulation, with evidence of
maladaptive circuit reorganization in the thalamocortical circuit. We test
the hypothesis that dTBI results in a burst of synaptogenic marker ex-
pression in the somatosensory cortex (S1BF), which would define the
time-frame of circuit reorganization. Adult male Sprague-Dawley rats
underwent sham or moderate midline fluid percussion injury. At nine
time points over 2 months post-injury, biopsies from the S1BF were
processed for gene and protein expression of synaptogenic markers using
qPCR and automated capillary westerns. Initial studies have revealed a
significant change in gene expression of both pre-synaptic (synapto-
physin; SYN) and post-synaptic (post-synaptic density protein of 95 kDa;
PSD-95) markers in the S1BF. Both SYN and PSD-95 show bimodal
variations in gene expression over time; F(9,48)
=
3.923; p
=
0.0009 and
F(9,49)
=
4.184; p
=
0.0005, respectively. Protein quantification of SYN
and PSD-95 in the S1BF are ongoing. These studies will provide a better
understanding of the temporal profile of synaptogenic events after dTBI
in the S1BF. This knowledge will lend insight to the anatomical mech-
anisms by which circuit reorganization leads to late-onset sensory sen-
sitivity to whisker stimulation. Therapies to regulate injury-induced
synaptogenesis may mitigate neurological impairment.
Supported, in part by, ADHS14-00003606, NIH R03 NS-077098,
NIH R01 NS-065052, Science Foundation Arizona, PCH Mission
Support Funds
Keywords: Traumatic brain injury, Synaptogenesis, Circuit reor-
ganization, Primary somatosensory cortex
C2-06
DRD2 C957T POLYMORPHISM IS ASSOCIATED WITH IM-
PROVED 6-MONTH VERBAL LEARNING FOLLOWING
TRAUMATIC BRAIN INJURY
Ethan Winkler
1
, John Yue
1
, Adam Ferguson
1
, Thomas McAllister
2
,
Jonathan Rosand
3
, Phiroz Tarapore
1
, Mary Vassar
1
, Kevin Wang
4
,
Pratik Mukherjee
1
, Alex Valadka
5
, David Okonkwo
7
, Ramon Diaz-
Arrastia
6
, Geoffrey Manley
1
1
UCSF, Neurosurgery, San Francisco, USA
2
Indiana University, Psychiatry, Indianapolis, USA
3
HMS, Neurology, Boston, USA
4
University of Florida, Neuroscience, Gainesville, USA
5
Seton Brain and Spine Institute, Neurosurgery, Austin, USA
6
USUHS, Neurology, Bethesda, USA
7
University of Pittsburgh, Neurosurgery, Pittsburgh, USA
Traumatic brain injury (TBI) often results in variable clinical outcomes,
which may be influenced by genetic variation. A single-nucleotide
polymorphism in the dopaminergic receptor type d2 (
DRD2)
may influ-
ence cognitive deficits following TBI. However, associations with
DRD2
were more recently attributed to genetic variability within the adjacent
ankyrin repeat and kinase domain containing 1 protein (
ANKK1
). Here,
we utilize the Transforming Research and Clinical Knowledge in Trau-
matic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether
a novel
DRD2
C957T polymorphism (rs6277) influences outcome on a
cognitive battery 6-months following TBI – California Verbal Learning
Test (CVLT), Wechsler Adult Intelligence Test Processing Speed Index
Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in
128 Caucasian subjects show that rs6277 T-carriers associates with better
verbal learning and recall on CVLT Trials 1–5 (mean increase 5.0; 95%
CI [0.8 to 9.2], p
=
0.02), Short-Delay Free Recall (mean increase 1.3,
95% CI [0.1 to 2.6], p
=
0.04), and Long-Delay Free Recall (mean in-
crease 1.3, 95% CI [0.1 to 2.6], p
=
0.04), which persist after controlling
for age, education years, Glasgow coma scale on admission and, most
notably, genotype of at least one common SNP within
ANKK1
(rs1800497). No association was found between the rs6277 polymor-
phism and processing speed (mean increase 1.43 seconds; 95%CI [-4.1 to
7.0], p
=
0.61) or mental flexibility (mean decrease 16.1 points; 95% CI [-
34.3 to 2.2], p
=
0.08) on WAIS-PSI and TMT, respectively. Hence, the
DRD2
polymorphism rs6277 may be associated with better performance
on select cognitive domains independent of
ANKK1
following TBI.
Keywords: TBI, outcomes, DRD2, CVLT
C2-07
BRAIN HYPOXIA RESPONSIVE GENE EXPRESSION IN SE-
VERE TRAUMATIC BRAIN INJURY PATIENTS
Ava Puccio
1
, Richard Jordan
3
, James Lyons-Weiler
3
, David
Okonkwo
1
, Yvette Conley
2
1
University of Pittsburgh, Neurosurgery, Pittsburgh, USA
2
University of Pittsburgh, Nursing, Pittsburgh, USA
3
University of Pittsburgh, Biostatistics, Pittsburgh, USA
A-78