Page 88 - NNS 2014 Program & Abstract Book

AS induced by exposure to predator scent did not worsen per-
formance on the behavioral tasks following mCCI, but the mCCI
seemed to blunt the abnormalities on the open field activity testing
seen with AS alone.
Key words
acute stress, fear response, impact injury, TMT, traumatic brain in-
jury, trimethylthiazoline
B3-02
EFFECT OF AGING ON COGNITIVE OUTCOME AND
NEUROINFLAMMATORY RESPONSE AFTER TRAUMATIC
BRAIN INJURY
Chou, A.C.1–3, Morganti, J.M.2,3, Rosi, S.1–3
1Neuroscience Graduate Program, UCSF, San Francisco, USA
2Brain and Spinal Cord Injury Center, San Francisco, USA
3Departments of Physical Therapy Rehabilitation Science and Neu-
rological Surgery, UCSF, San Francisco, USA
Traumatic Brain Injury (TBI) can alter neuronal function and in-
flammatory responses even beyond the site of injury. TBI outcomes
are worse in elderly patients including higher fatality rates and greater
severity of TBI-related disabilities. In animal models recapitulating
TBI, aging predisposes exacerbated neuronal loss, inflammation, and
motor function acutely. However, no mechanism for age-related ex-
acerbation of TBI has been identified. In the current study we in-
vestigated the effect of aging on TBI-induced cognitive deficits and
neuroinflammatory response. TBI was induced by controlled cortical
impact over the right parietal cortex in 3 and 18 month old male mice.
Thirty days after injury, hippocampal-dependent learning and memory
functions were measured using the radial arm water maze (RAWM)
which consists of eight arms with an escape platform located at the
end of one arm. Our data demonstrates that both age and TBI in-
creases the number of errors that the animal commits to locate the
escape platform when compared to their respective young and sham
controls.
Many studies have shown that reducing the pro-inflammatory re-
sponse can alleviate TBI-induced outcomes. While acute pro- and
anti-inflammatory responses are exacerbated by age, it is unclear if the
pro-inflammatory response is prolonged or if the anti-inflammatory
response is diminished over time in old animals as compared to young
animals. We characterized the inflammatory response of the injured
brain in young and old animals by quantitative PCR on isolated mi-
croglia/macrophages from the injured hemisphere at a sub-acute time
point 7 days after injury. Our results demonstrate that 7 days after
injury there was a significant decrease in anti-inflammatory cytokine
and M2 macrophage expression in old animals compared to the
young. These data suggest an imbalance in the regulation of inflam-
mation in the aging brain which may sustain a proinflammatory en-
vironment after injury.
Key words
aging, cognition, mice, neuroinflammation
B3-03
FRONTAL LOBE INJURY AND PREFRONTAL CORTEX-
DEPENDENT FUNCTIONS IN MICE
Chou, A.C.1–3, Morganti, J.M.2,3, Jopson, T.D.2, Rosi, S.1–3
1Neuroscience Graduate Program, UCSF, San Francisco, USA
2Brain and Spinal Cord Injury Center, San Francisco, USA
3Departments of Physical Therapy Rehabilitation Science and Neu-
rological Surgery, UCSF, San Francisco, USA
Traumatic brain injury (TBI) is the leading cause of neurological
disability in the world. The majority of studies with open-skull TBI
mouse models have utilized injuries over the parietal cortex and
characterized hippocampal dependent functions and motor recovery.
However, TBI often results in damage in the frontal lobe and induces
chronic cognitive, emotional, and social behavioral sequelae that af-
fect the long-term outcome and quality of life of human patients.
Prefrontal cortex (PFC) functionality can be impaired after TBI as
illustrated through poor performance on the Wisconsin Card Sorting
Test (WCST) which assesses attentional and affective set shifting
behavior. Mice likewise can develop affective and attentional sets and
their ability to perform affective and attentional set shifting is dis-
rupted by neurotoxic lesioning of the orbitofrontal cortex (OFC) and
medial prefrontal cortex (mPFC) respectively. The set shifting para-
digm (SSP) can be employed in an analogous manner to the WCST to
determine region-specific functionality of the PFC in mice.
TBI was reproduced using controlled cortical impact in three
month-old male C57BL6/J mice to the right frontal lobe. Thirty
days after surgery, animals were tested on the SSP and the ele-
vated plus maze (EPM) to characterize PFC-mediated attentional
and affective set shifting and anxiety. The SSP demonstrated that
mice with a frontal TBI committed more errors during affective set
shifting but were comparable to sham control animals on attentional
set shifting implying an impairment of OFC function without al-
teration of mPFC function. The EPM revealed a trend for TBI an-
imals to spend less time in the open arm of the maze which suggests
greater anxiety in animals with a frontal lobe TBI though the data
was not significant. Neuron, astrocyte, and microglia/macrophage
numbers were then examined after behavioral testing to characterize
the injury.
Key words
animal model, cognition, prefrontal cortex, traumatic brain injury
B3-04
PRIMARY BLAST INJURY ELIMINATES LONG-TERM PO-
TENTIATION IN RAT ORGANOTYPIC HIPPOCAMPAL
SLICE CULTURES
Vogel III, E.1, Villacorta, J.1, Bass, C.R.2, Meaney, D.F.3, Morrison III, B.1
1Columbia University in the City of New York, New York, USA
2Duke University, Durham, USA
3University of Pennsylvania, Philadelphia, USA
Blast-induced traumatic brain injury (TBI) is of growing concern for
military personnel. This study investigated the effect of primary blast
loading on electrophysiological function within rat organotypic hip-
pocampal slice cultures.
Blast injury was initiated with a compressed-gas driven shock tube.
Electrophysiological recordings were acquired 4–6 days following
injury using 60-channel microelectrode arrays. Three functional
measures (stimulus-response [S/R], paired-pulse [PP], long-term po-
tentiation [LTP]) were recorded following either a sham, mild
(336 kPa/0.84 ms/87 kPa$ms) or moderate injury (424 kPa/2.31 ms/
248 kPa$ms). Stimulating with increasing current and fitting the
voltage response to a sigmoid function generated S/R data. PP ratios
were produced by injecting two successive electrical stimuli with
increasing interstimulus intervals (ISIs) and dividing the amplitude of
the second response by the first at each ISI. LTP was induced in CA1,
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