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The lack of reproducibility in many areas of science, including spinal
cord injury (SCI) research, is due in part to the lack of common reporting
standards. Over the past three years an ad hoc consortium of scientists has
developed a minimum information reporting standard for SCI experi-
ments, called Minimum Information About an SCI Experiment
(MIASCI, J Neurotrauma. 2014 Jul 11. PMID: 24870067). The latest
version of MIASCI contains 13 sections: investigator, organism, surgery,
perturbagen, cell transplantation, biomaterials, histology, immunohisto-
chemistry, imaging, behavior, biochemistry, molecular biology, and data
analysis and statistics. For each of these sections, MIASCI enables sci-
entists to capture essential metadata about the study design, materials and
methods. The purpose of MIASCI is to improve transparency of re-
porting and to encourage the use of best practices. A secondary benefit is
to facilitate the aggregation and automated interrogation of diverse da-
tasets using a formal standard language. Thus, a parallel effort is un-
derway to develop an ontology about SCI: the RegenBase ontology.
Expanding RegenBase by incorporating MIASCI concepts facilitates
paper curation and knowledge creation. We will present MIASCI con-
cepts, show integration with the RegenBase Ontology and briefly de-
scribe recent work using MIASCI to annotate published papers studying
the effect of kinase inhibitors on SCI recovery.
Acknowledgments
NINDS NS080145 and NICHD HD057632
Keywords: ontology, database, reporting standard, informatics, re-
producibility
S01 Clinically Relevant Models of Neuroinflammation
after TBI
S01-01
NEUROINFLAMMATION IN THE DEVELOPING BRAIN
AFTER INJURY
Sujatha Kannan
Johns Hopkins University SOM, Pediatric Anesthesiology & Critical
Care Medicine, Baltimore, USA
Inflammation in the central nervous system, mediated by activated
microglia and astrocytes, is implicated in the development of several
neurologic disorders in both children and adults. Microglial function
is unique in the immature brain due to its role in normal develop-
ment related to white matter development and synaptic pruning.
Microglia are found in large numbers in the white matter tracts early
in childhood and move to the cortex later in life. Activation of glia
during vulnerable periods in development due to an insult/injury
may lead to an exaggerated inflammatory response that can result in
ongoing injury and chronic immune dysregulation. Strategies to
target microglia/astrocytes and treat neuroinflammation can poten-
tially not only slow disease progression, but also promote repair and
regeneration, enabling normal development and maturation of the
brain. We have previously demonstrated that intravenous adminis-
tration of a dendrimer-drug nanoparticle system selectively targets
and accumulates in activated microglia in the brain of newborn
rabbits with neuroinflammation and CP, resulting in significant im-
provement in motor function and myelination, attenuation of acti-
vated microglia, and decrease in neuronal injury by 5 days. A better
understanding of the role and timing of the neuroinflammatory re-
sponse in the immature brain after TBI is crucial for targeting ap-
propriate dendrimer-drug to activated microglia for modulating the
immune response.
Keywords: Microglia, Nanotechnology, Pediatric TBI, Dendrimer
S01-02
FRONTAL LOBE INJURY AND HIGHER-ORDER COGNI-
TIVE FUNCTIONS.
Catharine Winstanley
UBC, Psychology, Vancouver, Canada
Preclinical models of the psychiatric complications resulting from TBI
are urgently needed to facilitate the development of effective thera-
peutics. The frontal cortex is heavily implicated in many of the disor-
ders that manifest after TBI, including major depression, bipolar
disorder and impulsive aggression, and is often damaged by the impact.
We therefore aimed to determine the effects of TBI targeting the frontal
cortex (fTBI) in rats using a cognitive behavioral test commonly used to
model psychiatric symptoms. 30 male Long Evans rats were trained to
perform the five-choice serial reaction time task, in which subjects
respond to the brief presentation of a cue light in one of five distinct
apertures in order to earn sugar reward. This paradigm is highly sen-
sitive to frontal cortex damage, and provides well-validated measures of
visuospatial attention, motivation and motor impulsivity. We then used
the controlled cortical impact (CCI) method to induce different seve-
rities of fTBI, from severe to moderate (
*
50% of severe impact) and
milder CCI (
*
10% of severe impact). fTBI decreased accuracy of
target detection and increased motor impulsivity. Although each se-
verely injured animal continued to show substantive impairments across
all measures, 65% of animals that received a mild fTBI, and 35% of
those in the moderate fTBI group, showed dramatic improvements in
accuracy over 3 weeks to within 15% of their premorbid baseline. In
contrast, the performance of non-recovered animals overlapped with
that observed following severe fTBI, despite receiving only a mild or
moderate injury. Ex vivo analysis of cytokine expression revealed
strong correlations between levels of IL-6 and IL-10 with lesion size,
and the size of the lesion was also a good predictor of the level of
cognitive impairment. However, levels of IL-12 significantly correlated
with levels of impulsivity and inattention independent of lesion size,
suggesting that this immune signaling molecule may be contributing to
cognitive impairment via a unique and potentially druggable pathway.
Establishing this model in rats opens up the possibility for research into
biomarkers predictive of cognitive recovery or impairment.
Keywords: impulsivity, attention, cytokine
S01-03
TREATMENTS TO TARGET NEUROINFLAMMATION
Cesar Borlongan
University of South Florida Morsani College of Medicine, Neuro-
surgery and Brain Repair, Tampa, USA
Traumatic brain injury (TBI) is now recognized as a chronic injury with
multiple secondary cell death events, including neuroinflammation. I
discuss here two novel concepts of neuroinflammation-based therapies in
TBI. First, exogenous stem cells form ‘‘biobridges’’ that facilitate the
proper migration of endogenous stem cells from the neurogenic niche to
the site of injury following the controlled cortical impact model of TBI in
adult rats. Such exogenous stem cell-paved biobridges are enriched with
extracellularmatrix (ECM) stabilizing the structure and organization to the
injured tissues and also guiding the migration of and intercellular com-
munication with the endogenous stem cells. Our results indicate that the
injured brain not only presents with abnormal composition and structure of
the ECM that contributes to the failure of directed endogenous cell mi-
gration towards the injured site, but that TBI-mediated disruption of ECM
amplifies neuroinflammation ultimately hindering the homing of endog-
enous stem cells to the damaged tissue. Accordingly, treatments such as
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