Page 68 - NNS 2014 Program & Abstract Book

database. Data-driven drill-down into subject clusters showing robust
multifaceted forelimb recovery revealed enrollment in a placebo-
controlled dose response study of soluble tumor necrosis factor
receptor-1 (sTNFR1). Correction for robust effects of sTNFR1 in the
dataset uncovered significant detrimental effects on tissue sparing
from preclinical controlled trials of minocycline and methylprednis-
olone. Taken together, these results provide a proof-of-concept il-
lustration that TDA and similar big-data analytics may be valuable
screening tools of promising preclinical trials prior to replication and
translation into clinical trials. Funding: NIH grants NS067092,
NS069537, NS038079, NS031193, AG032518, NS079030; Neilsen
Foundation 224308; Wings for Life Foundation WFLUS008/12;
NYSCoRE CO19772.
Key words
bioinformatics, spinal cord injury, syndromics, topological data
analysis
A3-04
TOWARDS PRECLINICAL SENSORY COMMON DATA
ELEMENTS IN SPINAL CORD INJURY
Haefeli, J.1, Nielson, J.L.1, Guandique, C.F.1, Liu, A.W.1, Anderson,
K.D.2, Oswald, S.3, Beattie, M.S.1, Bresnahan, J.C.1, Ferguson, A.R.1
1University of California San Francisco, San Francisco, USA
2University of Miami, Miami, USA
3University of California Irvine, Irvine, USA
Translational spinal cord injury (SCI) research is challenged by a lack
of cross-species common data elements. Additionally, there is not a
clear strategy for broad monitoring of both sensory and motor out-
comes to screen for maladaptive plasticity, potentially resulting in
neuropathic pain. Efforts linking sensory and pain-related outcomes
across species are crucial to relate knowledge of mechanism gained in
preclinical research to clinical signs and symptoms. To this end, we
recently developed the Visualized Syndromic Information and Out-
comes for Neurotrauma–SCI (VISION-SCI) database to consolidate
sensory, motor, histopathological, and health outcomes within a multi-
center, multi-species database. The present study focused on curated
sensory outcomes in VISION-SCI, whereby prior work has included
motor outcomes. VISION-SCI currently incorporates data from 435
mice, 2225 rats and 59 monkeys. Within the rat population, 59.1%
(n = 1315) have motor outcomes, whereas only 10.2% (n = 227) have
sensory measures. Of the rats that received sensory testing, 96.5%
were also assessed for motor function. Sensory assessments included:
forepaw (FP) and hindpaw (HP) von Frey hair (VFH) testing (FP:
56.4%; HP: 95.6%), cold sensitivity (FP: 0%; HP: 7%), segmental
(4.8%) and supra-segmental (4.8%) responses to dermatomal VFH
stimulation. Despite the predominance of motor outcomes in the da-
tabase, nearly all studies with sensory function were also assessed for
motor recovery, with HP VFH testing being the most common sensory
measure collected. The current findings highlight the need for inte-
grating further sensory measures into the database, both from addi-
tional studies and species to reveal translational patterns of sensory
function. The long term goal of these efforts is to provide an analytical
pipeline to pave the way for improved cross-species sensory testing,
and accelerate translational research. Funded by: NIH: NS067092,
NS079030, NS069537, NS038079, NS031193, AG032518, NS-07291,
NS-3-2354; NYSCoRE-CO19772, Wings for Life WFLUS008/12 and
Craig H. Neilsen 224308.
Key words
database, sensory system, spinal cord injury, translational research
A3-05
ADVANCED MRI OF THE RAT CERVICAL SPINE FOL-
LOWING THORACIC CONTUSION SCI
Zakszewski, E. , Schmit, B., Kurpad, S., Budde, M.
Medical College of Wisconsin, Milwaukee, United States
Magnetic resonance imaging (MRI) is the state of the art approach for
assessing tissue viability following spinal cord injury (SCI). However,
meaningful imaging metrics are needed to evaluate and monitor injury
recovery. Often, the placement of hardware to stabilize the spinal
column prohibits followup MRI at the site of injury, but our previous
studies demonstrated that remote measures are promising markers of
injury and recovery. In this study, cervical spinal cords of rats with a
thoracic SCI were imaged using diffusion MRI and T2 to identify
remote makers of SCI.
Rats underwent a moderate thoracic injury using a weight-drop
device and were imaged on a 9.4T MRI at 2 and 30 days post-injury
along with non-injured controls. Diffusion weighted imaging was
performed along 2 directions (parallel and perpendicular to the spinal
cord axis) using 8 diffusion weighting factors (b-values) up to 3500
mm2/s. T2 imaging was performed with a multiple spin-echo se-
quence with 42 echos and 6.5 ms echo spacing. DWI was analyzed for
diffusivity, anisotropy, and metrics that reflect the non-gaussian be-
havior of the DWI signal, including kurtosis and bi-exponential fitting.
The MERA software package was used to derive quantitative T2
(qT2) data, by calculating the myelin water fraction (MWF), tissue
water fraction (TWF), and fat water fraction (FWF) based on the
spectrum of signal vs. echo time. Groupwise differences were iden-
tified using Student’s T-tests.
Using the conventional diffusion MRI analytical model for white
matter, no group differences were evident. Likewise, T2 values of the
white matter were not significantly different between groups. How-
ever, measures of diffusion non-gaussian behavior were significantly
elevated at 2 days after SCI compared to the control and day 30
measures. The T2 metrics demonstrated a similar trend of increased
FWF at the day 2 timepoint although the change was not significant.
Collectively, the results indicate disrupted water balance and mi-
croscopic changes in the cervical cord following a thoracic injury. The
advanced MRI measures here may be useful for evaluating and
monitoring patient injury and recovery following SCI.
Key words
contusion, diffusion imaging, magnetic resonance imaging, spinal
cord injury
A4-01
GFAP FRAGMENT BIOMARKERS AFTER TBI: EVIDENCE
FOR ACUTE ASTROCYTE PATHOLOGY
Huang, X.1,4, Glushakova, O.2 , Mondello, S.3, Van, K.1 , Hayes, R.2,
Lyeth, B.1
1University of California, Davis, USA
2Banyan Biomarkers, Inc., Alachua, USA
3University of Messina, Messina, Italy
4The Second People‘s Hospital of Shenzhen, Guangdong, China
Astrocytes play important roles in normal brain function and com-
munication. Recent findings indicate that astrocytes may be acutely
damaged after ischemic and traumatic brain insults. The objective of
this study was to determine the time course of biomarkers of astro-
cytic damage over the first 24 hours after experimental TBI. Twenty-
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