Page 151 - NNS 2014 Program & Abstract Book

sub-arachnoid spaces, contusion position relative to nerve roots, la-
minectomy size, temperature, and minor deviations of impact angles.
The percentage difference in preserved axons between those with and
without weight supported locomotor recovery is narrow and there are
inherent limits to control of variables that influence lesion severity.
Key words
axonal sparing, efficacy, hemodinamics, somatosensory evoked po-
tential, spinal cord injury, ultrasound
D2-17
LONGITUDINAL PROFILE OF SENSORIMOTOR DEFICITS
FOLLOWING SINGLE AND REPEATED PROJECTILE
CONCUSSIVE INJURY (PCI)
Mountney, A., Rho, C., Yang, W., Flerlage, J., Yarnell, A.,
Cartagena, C., Schmid, K., Bliese, P., Tortella, F.C., Shear, D.A.
Walter Reed Army Institute of Research, Silver Spring, MD
Mild traumatic brain injury (mTBI) is a significant concern for the
civilian and military populations. Previously, we developed a device
which produces a non-invasive projectile concussive impact (PCI)
modeling mild close-head concussive injury in rats. This study evalu-
ated the injury severity profile of sensorimotor dysfunction following
single and repeated mTBI. Anesthetized rats were subjected to a single
PCI injury (sPCI), repeated PCI (rPCI, 4 impacts, 1 h apart) or anes-
thesia (sham). Neurofunctional deficits were evaluated using the revised
neurological severity scale (NSS-R), the rotarod test, and CatWalk gait
analysis system. Results of NSS-R testing revealed significant neuro-
logical deficits in animals exposed to either single or repeated PCI at
1 h and 4 h post-injury (p < 0.05 vs. sham) that resolved by 24 h.
Animals were tested for motor/balance abilities on an accelerated
version of the rotarod task at acute (15 m, 1 h, 24 h) and subacute (7 and
14 d) post-injury time points. Rats exposed to a single PCI showed a
trend towards worse performance at 15 m post-injury that resolved by 1 h
post-injury. Animals exposed to repeated PCI showed significant motor
deficits at 15 m (vs. sham) and 1 h post-injury (vs. sham and sPCI) that
resolved by 24 h post-injury. Comprehensive gait analysis measurements
were taken prior to injury (baseline) and at 2 h, 24 h, 72 h, 9 d and 28 d
post-PCI. Animals exposed to a single PCI showed deficits on a limited
number of dynamic gait walk parameters at 2 h post-injury that were
resolved by 24 h post-PCI. In contrast, repeated PCI produced significant
deficits across 28 separate parameters, the majority of which were sus-
tained out to 72 h post-injury, but all of which resolved by 9 d post-PCI.
Collectively, these results indicate that significant, albeit subtle, senso-
rimotor deficits are evident following a single PCI with more sustained
deficits caused by repeated PCI. Further work is needed to evaluate the
effects of repeated PCI exposures spaced at variable inter-injury inter-
vals. Funded by CDMRP/DHP Grant W81XWH-12-2-0134.
Key words
gait analysis, mild TBI, motor/balance, neuropathology
D2-18
REPETITIVE MILD TRAUMATIC BRAIN INJURY MICE
EXHIBIT STRUCTURAL AND HISTOPATHOLOGICAL AL-
TERATIONS AND LONG-TERM BEHAVIORAL CHANGES
Yang, Z.Y., Morgan, D., Perez, P., Strang, K., Lin, F., Febo, M.,
Wang, K.
University of Florida, Gainesville, USA
Mild traumatic brain injuries (TBI), alternatively referred to as con-
cussions, are common in athletes, military personnel, and the elderly.
Increasing evidence indicates that these injuries have long-term health
effects. We developed a mouse model of repetitive closed head injury
(rCHI), which closely mimics real life repetitive mTBI in human.
Experimental brain injury was induced using a cortical impactor de-
vice mounted with a rubber coated metal tip, which is positioned
centrally above the sagittal-suture midway. Mice were assessed at 1,
7, and 30 days post-injury for brain structural alteration with magnetic
resonance imaging (MRI). To assess histological changes following
mTBI, the glial fibrillary acidic protein (GFAP) and microglial Ionized
calcium binding adaptor molecule 1 (Iba1) were monitored. Using a
variety of cognitive and behavioral tests (rotarod, grip strength, Morris
water maze (MWM), elevated plus maze and forced swimming test)
we assessed the short- and long-term behavioral sequelae of rCHI.
Our MRI results showed an initial lowering of apparent diffusion
coefficient (ADC) values and a decrease in T2 at 24 h after injury and
no difference was observed by 30 days post-injury. Activated mi-
croglia (cortex) and astrocyte (hippocampus and corpus callosum)
were observed from 7 post-injury, but no changed was found after 30
days post-injury. Significant impairments in motor deficits and neu-
romuscular function were observed 24 h post-injury, but no differ-
ences were found at 7 days post-injury. Significant differences were
observed between the injured mice and the controls in both the ele-
vated plus maze (day 30: p < 0.05; day 60: p < 0.05)) and forced swim
test (day 60: p < 0.05), which showed a depression- and anxiety-like
state in the injured mice. In MWM, animals received rCHI showed
spatial learning and memory deficit when tested at 30 days after in-
jury. Our results indicate that repetitive mTBI induces short-term
brain structural and histological alterations as well as motor impair-
ment, and profound and long-lasting learning and memory impair-
ments, accompanied by a depression- and anxiety-like behaviors.
Key words
anxiety, cognitive function, depression, mild TBI, MRI
D2-19
CHARACTERIZATION OF CCI USING HIGH SPEED IMA-
GING
Kim, Y., Ozl, J., Fortin, L., Fu, A., Tucker, L.B., McCabe, J.T.
Uniformed Services University of the Health Sciences, Center for
Neuroscience and Regenerative Medicine, Bethsda, USA
Controlled cortical impact (CCI) is a widely used preclinical model
for the study of traumatic brain injury (TBI). CCI has been employed
to understand biomechanical and physiological mechanisms of TBI,
behavioral responses, as well as to test potential therapeutic treat-
ments. Recent discussion in the literature emphasizes the need for
improved ‘‘methods-reporting’’ in preclinical research (Landis, et al.,
2012 Nature, 490:187; McNutt, 2014 Science, 343:229). Two CCI
impact actuators of the same model (Impact One, Leica) were used
with a 3-mm impactor tip, 100 ms dwell time, and impact penetration
depth controlled by changing the position of a stereotaxic frame.
Poron cushioning and a mouse brain with craniotomy were used to
record CCI impactor tip with a high speed digital camera (Y3-S1, IDT
Inc.). In the initial *15ms after activation, the impactor tip makes two
or three distinctive advances before it reaches the desired depth setting
for full extension. In the 1st and 2nd advances, the tip extended *50%
and 80% of the targeted distance, indicating that a single activation
results in three impact events. Impactor tip velocity on the 1st ex-
tension was normally faster than the preset values. The velocity of the
tip on the subsequent extensions were significantly slower. Excluding
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