OC3-03
DEVELOPMENT OF A CERVICAL SPINAL CORD CONTU-
SION MODEL IN NON-HUMAN PRIMATES
Salegio, E.
1
, Sparrey, C.J.
2
, Camisa, W.
3
, Rosenzweig, E.S.
8
,
Strand, S.C.
4
, Moseanko, R.
4
, Hawbecker, S.
4
, Nout, Y.S.
5
, Ma, X.
1
,
Zdunowski, S.
6
, Talbott, J.
1
, Buonocore, M.
4
, Sonico, J.
4
, Nielson, J.L.
1
,
Tam, H.
2
, Leasure, J.
3
, Buckley, J.
3,7
, Ferguson, A.R.
1
, Edgerton, V.R.
6
,
Tuszynski, M.H.
8
, Beattie, M.S.
1
, Bresnahan, J.C.
1
1
Brain & Spinal Injury Center, UCSF, SF, USA
2
Simon Fraser University, Surrey, Canada
3
St Mary’s Medical Center, SF, USA
4
CA National Primate Research Center, UC Davis, CA, USA
5
Colorado State University, FC, USA
6
UCLA, LA, USA
7
University of Delaware, Newark, USA
8
UCSD, SD, USA
A growing number of potential treatment approaches for spinal cord
injury (SCI) have been developed using rodent models, but successful
translation of treatments to human SCI has been fraught with challenges.
An intermediate step in this process has been identified by the field
supporting the use of a non-human primate (NHPs) model of preclinical
SCI. Using finite element analysis to scale up a unilateral cervical con-
tusion injury in the rat to NHPs, we have established a contusion injury
protocol that has many features of human cervical SCI. Furthermore, this
contusion model is supported by detailed behavioral, electrophysiological
and anatomical outcomes. Under deep anesthesia, nine rhesus ma-
caques received a unilateral contusion SCI at vertebral level C5 using a
friction-free actuator (Model 200N LM1, Bose Corp) with a 4mm di-
ameter impounder. Impact parameters were pre-calibrated
in vitro
using
a silicon-based surrogate cord, producing a wide range of injuries. Walk-
ing, climbing, and object manipulation were assessed during open-field
testing in all subjects. Skilled hand function, electromyogram analysis,
sensory testing, corticospinal tract tracing and magnetic resonance imaging
were also performed in a subset of animals. A high correlation between
peak force at impact and behavioral outcomes indicates the predictability
of the method for producing controlled injuries that can be used to test
treatments. Supported by NIH (R01-NS042291, R01-NS067092, F32-
NS079030), VA (B7332R), & The CH Neilsen Foundation.
Key words
contusion injury, non-human primates, pre-clinical model, spinal cord
injury
OC4-01
VIBRATION EXPOSURE LIMITS FOR NEUROTRAUMA
PATIENTS DURING MEDICAL TRANSPORT: OVERVIEW
Barazanji, K.
1
, Mayer, A.
2
, Kinsler, R.
1
, Wanner, I.
3
, Matchett, A.
2
,
Rahmatalla, S.
4
, Wilder, D.
4
, Kwon, B.
5
, Cripton, P.
5
, Chambers, P.
6
,
Reynolds, D.
7
1
U.S. Army Aeromedical Research Laboratory, Fort Rucker, USA
2
Lovelace Respiratory Research Institute, Albuquerque, USA
3
University of California, Los Angeles, USA
4
University of Iowa, Iowa City, USA
5
University of British Columbia, Vancouver, USA
6
Marketing Assessment, Inc., Sterling, USA
7
University of Nevada, Las Vegas, USA
Anecdotal observations in the field reported severe pain experienced by
neurotrauma patients when subjected to bumpy and high vibration ground
and air medical transport. The literature indicates that vehicle vibration
due to medical transport may be affecting medical outcomes. The goals of
our efforts are to (1) Characterize the effects of transport on a swine
model of traumatic brain injury (TBI) and spinal cord injury (SCI), (2)
Characterize the healthy human biodynamic response under similar
transport modes, (3) Identify TBI/SCI biomarkers from behavioral, his-
tological, imaging, and physiological measures, and (4) Develop the
dose-response relationship and determine the vibration exposure limit for
injured humans. The TBI mechanism is accomplished through blast ex-
posure and the SCI is produced surgically similar to the University of
British Columbia model. The TBI/SCI model is exposed to realistic
ground and air medical transport scenarios. The tested animals are divided
into four groups: (1) sham group, (2) TBI/SCI
+
transport, (3) TBI/SCI
and 4) SCI
+
transport. Standard military medical transport procedures are
practiced for immobilizing and securing the TBI/SCI model. Physiolo-
gical measurements and vehicle vibration throughout the patient litter
support system to include the animal model are recorded. X-ray images,
MRI, and neurologic evaluation are conducted before and after each
exposure. Various immunohistochemical and other CNS stains are used
to validate astrocyte-released injury biomarkers in swine CSF. Vibra-
tion transmissibility of the patient support system in a military heli-
copter is measured using supine healthy humans. The transfer functions
measured for the injured animals and the healthy humans are trans-
formed to determine vibration exposure limit criteria relevant to neu-
rotrauma patient transport.
Key words
immobilization, medical transport, vibration
OC4-02
DISRUPTION OF AUTOPHAGY FLUX FOLLOWING SPINAL
CORD INJURY IN GFP-LC3 REPORTER MICE
Liu, S.
2
, Remenapp, C.
1
, Sarkar, C.
1
, Koh, E.Y.
2
, Wu, J.
1
,
Lipinski, M.M.
1
1
University of Maryland School of Medicine, Department of An-
esthesiology, Shock, Trauma and Anesthesiology Research (STAR)
Center, Baltimore, MD
2
University of Maryland School of Medicine, Department of Ortho-
paedics, Baltimore, MD
Autophagy is a lysosome-dependent intracellular degradation process.
It plays an essential role in cellular homeostasis as well as a protective
function against a variety of conditions, including neurodegeneration.
Up-regulation of autophagy has been detected after SCI, but its
mechanisms and function remain unknown. Additionally, processivity
of autophagic degradation (flux), a crucial parameter that can radically
alter the function of autophagy, has not been determined after acute
SCI. We assessed levels of autophagy and autophagy flux after mod-
erate contusion SCI in transgenic mice expressing autophagy reporter
GFP-LC3. Our data indicated that autophagy marker LC3-II was in-
creased starting 3 hours after injury and remained elevated for at least
8 days. Accumulation of autophagosomes was confirmed by direct
imaging of GFP-LC3 in the injured spine sections. In the gray matter,
autophagosomes primarily accumulated in the ventral horn motor
neurons. In the white matter, GFP-LC3 signal accumulated in oligo-
dendrocytes and their precursors, and in activated microglia. In addition
to accumulation of GFP-LC3, in the same cells we also observed ele-
vated levels of the autophagy substrate, p62 and of ubiquitinated pro-
teins. This indicates that after SCI autophagosomes accumulate due to
inhibition of autophagic degradation rather than increased biosynthesis.
Levels of p62 and ubiquitinated proteins declined 1 week after injury,
indicating that at that time autophagy flux is likely restored. Although
under most conditions autophagy serves as a protective mechanism,
when flux is blocked, it may contribute to cell death. Consistent with
A-13
1...,35,36,37,38,39,40,41,42,43,44 46,47,48,49,50,51,52,53,54,55,...168