Page 157 - NNS 2014 Program & Abstract Book

Some studies have concluded that TBI results in anxiety, other reports
indicate no change, while others state that TBI decreases anxiety-like
states resulting in ‘‘risk-taking’’ behaviors. Differences in species/
strain of animal, experimental model and severity of TBI, time of
testing post-injury, testing conditions and criteria may obviously
contribute to the variability in conclusions. We investigated the re-
lationships between commonly-reported variables in the open field
(OF) and elevated zero maze (EZM) that are employed to draw
conclusions regarding anxiety-like states in rodents after TBI. Male
mice (C57BL6/J) that sustained TBI by controlled cortical impact
(CCI) were tested at multiple times post-injury in the OF and EZM. In
both injured and sham-operated animals coefficients of determination
were very low for time spent in the center of the OF and time in the
open quadrants of the EZM; commonly used measures of anxiety,
suggesting that the variability in these measures is largely unshared
and likely accounted for by other variables. Furthermore, correlations
between time spent in the center zone of the OF and time spent in
open quadrants of the EZM were greater when the animals were tested
for 60 minutes, suggesting that testing for shorter durations of time
represents behavior specific to habituation to the environment and
may not accurately represent exploratory and anxiety-like behaviors
that result from longer periods of testing. These results demonstrate
the difficulty of comparing the results of behavioral testing from ro-
dent TBI experiments, particularly when the studies employ different
apparatus and report different dependent measures.
Key words
animal testing, anxiety, behavior
D2-34
METABOLITE, HISTOPATHOLOGICAL AND FUNCTIONAL
CHANGES IN THE HIPPOCAMPUS AFTER BLAST EX-
POSURE
Ng, K.C.1, Wong, Y.C.1, Kan, E.M.1, Verma, S.K.2 , Prakesh, B.K.2,
Saramani, S.2 , Velan, S.S.2, Lu, J.1
1Combat Care Laboratory, Defence Medical and Environmental Re-
search Institute, DSO National Laboratories, Singapore, Singapore
2Magnetic Resonance Spectroscopy and Metabolic Imaging Group,
Singapore Bioimaging Consortium, A*STAR, Singapore, Singapore
Almost 80% of blast induced TBI cases reported in the military were
of mild severity where soldiers presented no external signs of injury
but whose brain may have been damaged and presented symptoms of
cognitive, physical and neuropsychiatric dysfunctions. This study
aims to investigate the effect of blast exposure and how it affects on
hippocampal function and memory.
Briefly, male Sprague Dawley rats were exposed to a single blast
at * 180kPa. The animal were evaluated before and after the injury
on the radial arm maze and subjected to longitudinal Single Voxel
Spectroscopy (SVS) 1H-MRS imaging using PRESS technique (voxel
size of 3.5 · 2 · 3.5 mm3) in the hippocampus. In addition, TUNEL
assay for apoptotic neurons and NeuN immunohistochemistry was
carried out on brain slices at - 3.8 mm bregma at stipulated post-blast
sacrifice timepoints (Day 1, Day 3, Day 5, Day 14, and Day 28 post-
blast).
In the hippocampus, there was a slight increase in TUNEL-im-
munoreactivity and the NeuN immunostaining showed shrunken and
distorted neurons at 24 h and 72 h after blast injury, which may be
indicative of either ischemic or physical injury. Transient memory
impairments in the radial arm maze were detected at day 4 and 5 after
blast injury. NAA metabolite level assessed by 1H-MRS was also
decreased at day 3 after blast injury which mirrors the decrease in
other CNS pathological conditions involving neuronal loss or dys-
function such as Alzheimer’s disease and stroke. A decrease in hip-
pocampal glucose was observed in the 1H-MRS spectrum at 3 days
post-injury which points towards a depressed CNS metabolism.
Overall, histopathological changes in the hippocampus coincide with
the transient functional changes after blast exposure.
Key words
behavioral changes, blast injury, H-MRS imaging, hippocampus
damages, metabolite changes
D2-35
CONTROLLED-CORTICAL IMPACT REDUCES RATS’
ABILITY TO SUSTAIN APPLICATION OF SUBMAXIMAL
FORCE
Choua, C., Schmid, A., Kim, L., Trieu, J., Machuca, D., Sterling, S.,
Shah, S., Khan, S., Pruitt, D., Rennaker II, R.L.
The University of Texas at Dallas, Richardson, TX
Traumatic brain injury (TBI) is an increasingly large health risk in the
United States and often results in a severe lack of motor control and
weakness. We have recently reported that experimental TBI in rats
induces a chronic impairment in maximal volitional forelimb strength.
Many activities of daily living, however, require consistent applica-
tion of controlled submaximal force rather than maximal force.
Therefore, we sought to investigate the effect of a controlled-cortical
impact (CCI) on rats’ ability to generate a submaximal level of force
over a sustained duration. Rats were trained using the isometric force
task to sustain a pull of at least 35 grams over 1 second in length.
After achieving proficiency at the task, rats’ received a CCI in motor
cortex contralateral to the trained limb and underwent 6 weeks of
post-lesion assessment. Preliminary results indicate that CCI results in
chronic deficits in rats’ ability to sustain submaximal force thresholds.
These results further characterize motor impairments resulting from
CCI and may provide an additional model in which to test future
therapies to enhance recovery from TBI.
Key words
controlled cortical impact, isometric force task, sustained force, TBI
D2-36
NEUROPATHOLOGICAL AND BIOCHEMICAL ASSESS-
MENT OF CHIMERA: A NOVEL CLOSED-HEAD IMPACT
MODEL OF ENGINEERED ROTATIONAL ACCELERATION
Namjoshi, D.R.2,1, Cheng, W.H.1, McInnes, K.3, Fan, J.1, Wilkinson,
A.1, Chan, J.1, Cripton, P.A.3, Wellington, C.L.1
1Department of Pathology and Laboratory Medicine, The University
of British Columbia, Vancouver, Canada
2Department of Mechanical Engineering and Orthopaedics, The
University of British Columbia, Vancouver, Canada
Despite promising outcomes from many preclinical studies, clinical
studies have failed to identify effective pharmacological therapies for
traumatic brain injury (TBI), suggesting that the translational potential
of preclinical models requires improvement. To address the challenge
of generating a simple and reliable model of rodent TBI, we have
developed a novel neurotrauma model called CHIMERA (Closed-
Head Impact Model of Engineered Rotational Acceleration) that fully
integrates biomechanical, behavioral, and neuropathological analyses.
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