1
Uniformed Services University of the Health Sciences, Department of
Anatomy, Physiology & Genetics, Bethesda, USA
2
Center for Neuroscience and Regenerative Medicine, Pre-Clinical
Studies Core, Bethesda, USA
A single concussive brain injury (CBI) can result in prolonged neu-
rological deficits in clinical populations, but functional impairments
following a single CBI are often difficult to detect in rodent models
using traditional behavioral tests, even in the acute time period fol-
lowing the injury. In this experiment, we employed Any-Maze cages
(Stoelting, Co.) to continuously monitor home cage activity, wheel
running and ingestive behaviors following CBI. Male and age-
matched, cycling female C57BL/6J mice were subjected to a closed-
skull concussive brain injury (CBI) delivered via a Leica ImpactOne
controlled cortical impact device. Following recovery of the righting
reflex, mice were placed into Any-Maze cages, where they remained
for three days, followed by testing in an open field and on the y-maze
test of spontaneous alternation behavior (working memory). The du-
ration of apnea following CBI was longer in female mice than in male
mice. The amount of time to appearance of the righting reflex was also
longer in female mice, but there did not appear to be a relationship
between duration of apnea and righting reflex recovery. CBI greatly
reduced activity in the home cages during the 24 hours following the
injury, as measured by decreased movement around the cage, de-
creased wheel running, and a large reduction in food and water intake.
These measures returned to the levels of sham controls within 48
hours following the injury. Injured animals had normal behavior in an
open field and unimpaired working memory performance in the
y-maze spontaneous alternation test three days following CBI. These
results suggest that an identical injury has greater immediate effects
on smaller female mice as assessed by duration of apnea and recovery
of the righting reflex, but changes in motivated behaviors are equally
impaired in both sexes and are resolved quickly.
Keywords: behavior, concussion, ingestion, circadian activity
D2-08
LOCALIZATION OF THE CORTICOSPINAL TRACT IN
PIGS: IMPLICATIONS FOR MODELLING TRAUMATIC
SPINAL CORD INJURY
Anna Leonard
1,2
, Joshua Menendez
4
, Betty Pat
2
, Mark Hadley
4
,
Robert Vink
3
, Candace Floyd
2
1
University of Adelaide, School of Medical Sciences, Adelaide, Aus-
tralia
2
University of Alabama at Birmingham, Department of Physical
Medicine and Rehabilitation, Birmingham, USA
3
University of South Australia, Division of Health Sciences, Adelaide,
Australia
4
University of Alabama at Birmingham, Department of Neurosurgery,
Birmingham, USA
Background:
Spinal cord injury (SCI) researchers have predomi-
nately utilized rodents for SCI modeling and experimentation. Un-
fortunately, the large number of developed novel treatments for SCI
using rodent models have failed to demonstrate efficacy in human
clinical trials. Recently, porcine models of SCI have been identified as
a valuable intermediary model for preclinical evaluation of promising
therapies to aid clinical translation. However, the localization of the
major spinal tracts in pigs has not yet been described. Determining the
similarity of the location of the corticospinal tract in pigs compared to
humans may therefore provide important evidence for the use of pigs
as a vital pre-clinical model.
Objective:
We aim to investigate the localization of the corti-
cospinal tract within the porcine spinal cord and determine the simi-
larity to human and rodent anatomy.
Methods:
Mature female domestic pigs (n
=
4, 60 kg) received
microinjections of fluorescent dextran tracers (Alexa Fluor, 10,000
MW, Life Sciences) into the primary motor cortex guided by a
STEALTH navigation stereotactic system. At 4 weeks post-tracer
injection animals were euthanized, the entire neuroaxis harvested and
processed for histological examination. Serial sections of the brain
and spinal cord were prepared, imaged and digitally reconstructed to
give a 3D visualization of the corticospinal tract location.
Results:
The corticospinal tract of pigs is located in the lateral
white matter, demonstrating greater similarity to human anatomical
structure than that of rodents.
Conclusion:
The corticospinal tract in pigs demonstrates anatom-
ical similarity to human, suggesting that the porcine model has im-
portance as a translational intermediary pre-clinical model.
Supported by: UAB Department of Physical Medicine and Re-
habilitation
Keywords: Spinal Cord, Tract Tracing, Porcine Model, Corticosp-
inal Tract
D2-09
BIOMECHANICAL AND FUNCTIONAL CHARACTERIZA-
TION OF CHIMERA IN AN APP/PS1 MODEL OF ALZHEI-
MER’S DISEASE
Kris Martens
1
, Wai Hang Cheng
1
, Dhananjay Namjoshi
1
, Peter
Cripton
2
, Cheryl Wellington
1
1
University of British Columbia, Pathology and Laboratory Medicine,
Vancouver, Canada
2
University of British Columbia, Mechanical Engineering and Or-
thopaedics, Vancouver, Canada
Background:
In addition to being a leading cause of disability in
young people, traumatic brain injury (TBI) is a risk factor for de-
mentia, including Alzheimer’s disease (AD). Notably, both amyloid
and tau neuropathology can develop after TBI. We recently developed
a novel rodent TBI model called CHIMERA (Closed-Head Impact
Model of Engineered Rotational Acceleration) that uses a non-
surgical procedure to precisely deliver defined impacts to an intact
head with unrestrained and reliable head movement. In C57Bl/6,
CHIMERA induces significant behavioral deficits, white matter in-
flammation, axonal damage, and endogenous tau phosphorylation.
Here we apply CHIMERA TBI to the APP/PS1 model of AD.
Objective:
To characterize acute biomechanical, behavioral, and
neuropathological outcomes of repetitive TBI using CHIMERA in
APP/PS1 mice.
Methods:
CHIMERA was used to induce two mild TBIs (0.5 J
impact energy), spaced 24 hours apart in 5-mo male APP/PS1 mice.
Head kinematics were assessed using high-speed videography
(5000 fps). Acute behavioral, histological, and biochemical outcomes
tests were conducted up to 48h post-injury.
Results and Discussion:
Head kinematic analysis showed peak
displacement of 41.8
–
3.7 mm, peak angular deflection of
2.3
–
0.4 rad, peak linear and angular velocities of 5.2
–
0.4 m/s and
314.0
–
169.6 rad/s, respectively, and peak linear and angular accel-
erations of 238.3
–
79.2
g
and 280.3
–
168.5 krad/s
2
, respectively. Im-
mediately post-TBI, APP/PS1 mice experienced a prolonged loss of
righting reflex compared to sham-operated APP/PS1. Behavioral
analysis at 48h revealed increased neurological deficits (neurological
severity score), and poorer motor coordination (Rotarod) in injured
A-103