NNS 2015 Program & Abstract Book

Uniformed Services University of the Health Sciences, Department of

Anatomy, Physiology & Genetics, Bethesda, USA

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

, Betty Pat

, Mark Hadley

Robert Vink

, Candace Floyd

University of Adelaide, School of Medical Sciences, Adelaide, Aus-

tralia

University of Alabama at Birmingham, Department of Physical

Medicine and Rehabilitation, Birmingham, USA

University of South Australia, Division of Health Sciences, Adelaide,

Australia

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

, Wai Hang Cheng

, Dhananjay Namjoshi

, Peter

Cripton

, Cheryl Wellington

University of British Columbia, Pathology and Laboratory Medicine,

Vancouver, Canada

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

and 280.3

–

168.5 krad/s

, 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

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