Page 67 - NNS 2014 Program & Abstract Book

A3-01
ISOLATED THORACIC SPINAL CORD CONTUSION IN
MICE INDUCES COGNITIVE AND EMOTIONAL BEHAVIOR
IMPAIRMENTS
Zhao, Z., Stoica, B.A., Faden, A.I., Wu, J.
University of Maryland, Department of Anesthesiology, Baltimore,
USA
Clinical studies have reported cognitive and emotional deficits after spinal
cord injury (SCI). Roth et al. demonstrated that 40–60% of SCI patients
show impairment in attention, concentration, memory, learning, and/or
problem-solving ability. The cause of the cognitive deficits in SCI pa-
tients has been debated, because of potentially confounding factors such
as concurrent traumatic brain injury (TBI). Studies that addressed this
issue by focusing on SCI cases without signs of TBI have confirmed that
these patients also show impairments in cognitive function. Yet, the fact
that SCI can cause neurodegeneration in the brain, or that such changes
can negatively impact long-term cognitive outcomes or emotional state is
still unapreciated by the at-large research and clinical communities. It is
known that cognitive/emotional impairments are detrimental to SCI pa-
tients not only in their own right but because they can compromise
rehabilitation. Here we examined effects of isolated thoracic SCI in mice
on cognition, depression, and brain neurodegeneration. To determine
whether cognitive/emotional impairments increase as a function of injury
severity we exposed mice to sham, mild, moderate, or severe SCI and
evaluated performance on a variety of neurobehavioral tests that are less
dependent on locomotion. We showed that locomotor function (BMS
scores) was reduced in an injury severity manner. Cognitive impairments
in the tests of Y-maze, novel objective recognition, and step-down fear-
conditioning increased with injury severity at two months post-injury.
SCI also caused deficits in emotional behavior as quantified in the sucrose
preference, tail suspension, and forced swim test, in a manner dependent
on injury severity. Stereological analysis demonstrated significant chronic
neuronal loss in the cerebral cortex, thalamus, and hippocampus in the
moderate/severe SCI groups. Our data suggest that SCI induces chronic
neurodegeneration in important brain regions associated with cognitive
decline and depression. Thus, these findings provide the experimental
confirmation of clinical evidence suggesting SCI-related cognitive/emo-
tional deficits, considerably revising concepts about the nature of SCI as a
focal acute neurodegenerative disorder.
Key words
brain, cognitive impairment, depression, neurodegeneration, spinal
cord injury
A3-02
MINIMUM INFORMATION ABOUT A SPINAL CORD
INJURY EXPERIMENT (MIASCI): CONCEPTS AND
INTEGRATION WITH THE REGENBASE ONTOLOGY
Callahan, A.V.1, Sakurai, K.2, Abeyruwan, S.W.3, Ferguson, A.R.4,
Popovich, P.G.5, Visser, U.3, Bixby, J.L.2, Lemmon, V.P.2
1Stanford University, Stanford Center for Biomedical Informatics
Research, Stanford, United States
2University of Miami, Miami Project to Cure Paralysis, School of
Medicine, Miami, United States
3University of Miami, Department of Computer Science, Miami,
United States
4University of California, San Francisco, Brain and Spinal Injury
Center (BASIC), Department of Neurological Surgery, San Francisco,
United States
5Ohio State University, Center for Brain and Spinal Cord Repair and
the Department of Neuroscience, Columbus, United States
The lack of reproducibility in many areas of science, including spinal
cord injury (SCI) research, is due in part to the lack of common re-
porting standards. Over the past three years an ad hoc consortium of
scientists has developed a minimum information reporting standard
for SCI, called Minimum Information About an SCI Experiment
(MIASCI). Version 1.0 of the MIASCI contains 11 sections: investi-
gator, organism, surgery, perturbagen, cell transplantation, biomaterials,
histology, immunohistochemistry, imaging, behavior, and data analysis
and statistics. Each section has a number of data elements to be filled in
that detail essential metadata about the project, materials and methods.
Depending on a particular study, not all sections will apply. The purpose
of MIASCI is to improve transparency of reporting and to encourage the
use of best practices. A secondary benefit is to facilitate the aggregation
and automated interrogation of diverse datasets using a standard lan-
guage. Thus, a parallel effort is underway to develop an ontology about
SCI, the RegenBase ontology, and an associated knowledgebase. Ex-
panding RegenBase by incorporating MIASCI concepts facilitates lit-
erature curation and knowledge creation. We present MIASCI concepts,
show integration with the RegenBase ontology and present different
approaches to literature annotation. Querying the RegenBase knowl-
edgebase using the integrated ontology is also illustrated.
Acknowledgments
NINDS NS080145 and NICHD HD057632
Key words
knowledge representation, ontology, reporting standards
A3-03
DATA-DRIVEN DISCOVERY OF SYNDROMIC EFFICACY
FOR PRECLINICAL DRUG TRIALS IN CERVICAL SPINAL
CORD INJURY
Nielson, J.L.1, Irvine, K.A.2, Gensel, J.C.3, Huie, J.R.1 , Guandique,
C.F.1, Liu, A.W.1, Lin, A.1, Ratan, R.R.4 , Beattie, M.S.1, Bresnahan,
J.C.1, Ferguson, A.R.1
1Department of Neurosurgery, University of California, San Fran-
cisco, USA
2San Francisco VA-NCIRE, University of California, San Francisco, USA
3Department of Physiology, University of Kentucky, Lexington, USA
4Weill Cornell Medical College, Cornell University, White Plains
The growth of preclinical spinal cord injury (SCI) research over the
past few decades has produced a huge volume of data, but only few
replicable treatments. Often, data presented in published reports rep-
resents a fraction of the multiple measures used, varying from labo-
ratory to laboratory. Some of the difficulties in replication may be due
to this somewhat fractured approach. We are currently exploring a
more integrated big-data approach to yield new insights into recovery
from and treatments for experimental SCI, by reevaluating raw data
from multiple preclinical trials of cervical SCI. The present study
applied a novel multivariate analytic and visualization method known
as topological data analysis (TDA) to data from preclinical cervical
SCI studies. TDA facilitates rapid data integration, analysis, visuali-
zation and interpretation of multiple large datasets simultaneously,
promoting rapid data-driven discovery of robust therapeutic effects in
large, heterogeneous datasets. As proof-of-concept, data from 6
completed preclinical trials in rats receiving graded cervical
SCI (n = 159 rats) with matching functional and histopathological
outcomes (m = 340 variables) were mined from the VISION-SCI
A-35