41 / 198
reduced in STD at 6 hrs. Activity continued to be reduced at 24 hrs in
STD animals with no differences in KD animals. These results strongly
suggest that ketones improve post-TBI cerebral metabolism by providing
alternative substrates and through antioxidant properties, preventing
oxidative stress mediated mitochondrial dysfunction.
Acknowledgements
NFL Charities, UCLA Brain Injury Research Center, Marilyn and
Austin Anderson Fellowship, NS058489-01, NS27544
Keywords: traumatic brain injury, mitochondria, ketogenic diet,
oxidative stress, juvenile
T1-09
EXPERIMENTAL DIFFUSE TRAUMATIC BRAIN INJURY IN-
CREASES ASTROCYTE-SECRETED THROMBOSPONDIN-1
IN THE THALAMUS
Sarah Ogle
1,2,4
, Hazel May
1,5
, Rachel Rowe
1,2,3
, Benjamin
Rumney
1,5
, Steven Johnson
1,4
, P. David Adelson
1,2
, Jonathan
Lifshitz
1–3
, Theresa Thomas
1–3
1
UA, Medicine, Phoenix, USA
2
PCH, BNI, Phoenix, USA
3
VA, Research, Phoenix, USA
4
BUMC-Phoenix, Surgery, Phoenix, USA
5
University of Bath, Biology, Phoenix, UK
Publicity of neurological dysfunction induced after diffuse trau-
matic brain injury (dTBI) has highlighted the necessity to under-
stand the causative pathophysiology. In rodents, dTBI leads to
sensory sensitivity to whisker stimulation in the thalamocortical
circuit, similar to light and sound hypersensitivity experienced by
brain injury survivors. A proposed source of this morbidity is ma-
ladaptive circuit reorganization as a result of post-traumatic sy-
naptogenesis. After neurological insult, the developmental
synaptogenic protein thrombospondin-1 (TSP-1) would be primarily
secreted by activated astrocytes in the adult CNS. We hypothesize a
role for TSP-1 in mediating synaptogenesis after dTBI. For this
study, adult male Sprague-Dawley rats underwent sham or moderate
midline fluid percussion brain injury. At multiple time points post-
injury, gene and protein expression of TSP-1 were quantified in
thalamic biopsies using qPCR and automated capillary westerns.
TSP-1 gene expression increased over time (F(8,48
=
2.964;p
=
0.0089), with significance at 5 days post-injury (DPI) compared to
uninjured shams. Similarly, TSP-1 protein expression increases over
the first week post-injury (F(5,16)
=
3.972;p
=
0.0156), reaching
significance at 7DPI in comparison to sham. Additionally, tissue
sections were stained with glial fibrillary acidic protein (GFAP), a
marker of activated astrocytes. Thalamic GFAP pixel density in-
creased over time (F(3,12)
=
15.73;p
=
0.0002), with staining at 7
and 28DPI being greater than sham. This study identified a temporal
profile for TSP-1 gene and protein expression after dTBI that co-
incides with evidence of activated astrocytes in the thalamus. TSP1-
mediated synaptogenesis may play a pivotal role in thalamocortical
circuit reorganization which subsequently leads to injury-induced
neurological dysfunction. Understanding the temporal profile of
synaptogenic events after dTBI may allow for mitigation of neu-
rological dysfunction by pharmacologic and rehabilitative manipu-
lation Partially supported by ADHS14-00003606, NIH-R03 NS-
077098, NIH-R01 NS-065052, Science Foundation Arizona, PCH
Mission Support.
Keywords: Thrombospondin, Traumatic Brian Injury, Thalamus,
synapotogenesis
T1-10
PERIOPERATIVE HYPERTENSION PREDICTS WORSE
FUNCTIONAL RECOVERY FOLLOWING THORACIC
SPINAL CORD INJURY IN RATS
Jessica Nielson
1
, Cristian Guandique
1
, Aiwen Liu
1
, C. Amy Tovar
2
,
Wise Young
3
, Michael Beattie
1
, Jacqueline Bresnahan
1
, Adam
Ferguson
1
1
University of California San Francisco, Neurological Surgery, San
Francisco, USA
2
Ohio State University, Neuroscience, Columbus, USA
3
Rutgers University, W.M. Keck Center for Collaborative Neu-
roscience, New Brunswick, USA
Neurocritical care complications following spinal cord injury (SCI)
may have long-lasting effects on neurological recovery. Although
neurocritical care logs are maintained in animal research, they are
rarely considered as relevant predictors of outcome. We curated 20
years of animal SCI research care logs to build a translational
electronic medical record (trans-EMR) containing detailed data from
physiology and bloodwork measures. To maximize utility of trans-
EMR data for SCI decision-making, we applied topological data
analysis (TDA), which deploys ensemble machine learning in mul-
tidimensional space to heterogeneous, complex big-data. Data que-
ried from the VISION-SCI database (N
=
2719) included adult male
and female rats receiving graded thoracic bilateral SCI contusions
(T9; MASCIS impactor; 12.5, 25 and 50 mm). Inclusion criteria:
complete data for perioperative vitals (body temperature, heart rate,
blood pressure), blood gases, weight monitoring, bladder care, lo-
comotor function (1–6 weeks post-injury BBB scores) and terminal
tissue sparing (6 weeks) (N
=
334). TDA revealed a data-driven,
syndromic relationship between perioperative care and locomotor
recovery on a subset of the animals (N
=
72). Cross-validation of
TDA-identified patterns was performed on the remaining animals
(N
=
262) using an analytical workflow of TDA, a post-hoc repeated-
measures general linear model (GLM) and bivariate correlations.
TDA identified network dysfunction in BBB recovery, significantly
predicted by hypertensive episodes (MAP
>
140 mmHg) during SCI
operation. Cross-validation in the independent data-set revealed a
similar significant difference in BBB recovery inversely predicted by
MAP. GLM on BBB recovery revealed MAP significantly predicted
locomotion in both datasets, and correlational analyses confirmed an
inverse relationship. Together the data indicate that perioperative
hypertension predicts poor recovery following SCI, an effect size
greater than the drug effects in multiple preclinical trials. Funding:
Craig H. Neilsen Foundation 224308, NIH: NS067092, NS069537,
NS079030, NS032000, NS088475, Wings for Life Foundation
WFLUS008/12
Keywords: hypertension, spinal cord injury, topological data anal-
ysis, syndromics
T1-11
KINASES REGULATING GLUTAMATE TRANSPORTERS
ARE DIFFERENTIALLY ACTIVATED AFTER LATERAL
FLUID PERCUSSION
Jennifer McGuire
1
, Erica DePasquale
2
, Christopher Dorsett
2
,
Candace L. Floyd
2
, Robert McCullumsmith
1
1
University of Cincinnati, Psychiatry and Behavioral Neuroscience,
Cincinnati, USA
2
University of Alabama at Birmingham, Physical Medicine and Re-
habilitation, Birmingham, USA
A-5