Page 105 - NNS 2014 Program & Abstract Book

findings, together with an extended therapeutic window, offer
promise for translation to the clinical setting.
Funding: DOD-SC100140
Key words
neurogenic bladder dysfunction, spinal cord injury
C1-02
GENE EXPRESSION CHANGES IN RESPONSE TO SELE-
NIUM DIET IN SPINAL CORD INJURED RATS
Crowdus, C.A.1, Blalock, E.M.1, Yu, C.G.1, Power, R.F.2, Geddes, J.W.1
1University of Kentucky, Lexington, USA
2Alltech, Nicholasville, USA
Certain groups at high risk for spinal cord injury (SCI) groups may
benefit from a prophylactic supplement, such as dietary selenium,
that would intervene in the secondary neurodegenerative cascade
immediately following trauma. The high demand for selenium
within the CNS, as well as the synthesis of selenoproteins by
neurons and astrocytes suggests a critical role of selenium within
the brain and spinal cord. Selenium was supplemented in the diets
of female Sprague-Dawley rats prior to receiving a moderate (150
kdyn) contusive spinal cord injury or sham laminectomy. Twenty-
four hours following injury, 7 mm of spinal cord directly sur-
rounding the injury epicenter was collected from animals on both
diets, sham and injured. RNA was isolated from these tissues,
converted to cDNA, and utilizing the Affymetrix genome array
platform, hybridized to rat microarray genome chips with probe
sets representing 31,097 genes. Raw signal intensities from Affy-
metrix scanner were converted to gene expression summary values
using RMAExpress. Genes underwent a rigorous selection process,
which resulted in a 14,907 filtered gene list. These genes were
subjected to a 2-way ANOVA, and filtered further based upon a
Bonferonni correction for 3 tests using genes that met the criteria of
p < 0.017. The resulting list was sorted into templates based on
their expression patterns in the four treatment groups. A total of
4301 and 4812 genes were consistently down-regulated and up-
regulated, respectively, across diet groups in response to the injury.
Of particular interest, a template that isolated 78 genes specifically
down-regulated in the control injured group showed these pheno-
types rescued in selenium injured animals, including genes asso-
ciated with transcriptional regulation and cell cycle arrest.
Additionally, another template showed 111 genes up-regulated in
selenium injured animals when compared to control injured ani-
mals. These genes include pathways associated with DNA repair,
mitochondrial function, and protein turnover. These tools will help
us to understand mechanisms of selenium in the central nervous
system in response to injury.
Key words
dietary, gene expression, selenium, spinal cord injury
C1-03
EFFECT OF A GNRH AGONIST ON LOCOMOTION, GAIT
AND SPINAL CORD MORPHOLOGY IN RATS WITH SPINAL
CORD INJURY
Diaz-Galindo, C., Calderon-Vallejo, D., Hernandez-Jasso, I.,
Bautista, E., Salinas, E., Quintanar, J.L.
Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico
It has been reported that Gonadotropin-releasing Hormone (GnRH)
has neurotrophic effects, improves locomotor activity and urinary
function of rats with spinal cord injury (SCI). Our aim was to
determine whether administration of a GnRH agonist (GnRH-A)
improves locomotion, gait and spinal cord morphology in rats with
SCI.
Ovariectomized adult female Wistar rats were divided in five
groups. Sham SCI (Sham), control SCI treated with saline solution
(SS), SCI treated with GnRH-A at dose 1.2 lg/kg (GnRH-A 1),
5 lg/kg (GnRH-A 2) and 10 lg/kg (GnRH-A 3). The lesion was
performed using a compression model. A Fogarty catheter was
introduced at T-12 level and the catheter balloon was insufflated to
20 ll during five minutes. All animals were sacrificed 6 weeks later.
One day after SCI, GnRH-A was administrated three consecutive
days, and followed by an administration every 4 days during 6
weeks. One day after SCI, all groups were evaluated weekly ac-
cording to the BBB scale, gait (path time, distance and speed
stride) and spinal cord morphology (white and gray matter spared
area) by histochemistry.
We found that, at the sixth week, GnRH-A treatment improves
the movement, being a 40%, 35% and 41% of recovery in GnRH-A
1,2 and 3 respectively, while SS group was 7% only in the BBB
scale. In gait analysis, GnRH-A groups decreased the time, in-
creased both, distance and speed of the path compared to SS group.
According to the area of spared tissue, gray and white matter was
higher in treated groups compared to SS group, but only GnRH-A 2
had a significant difference. In conclusion, GnRH-A treatment
improves locomotion, gait, and the morphology of the spinal cord
in rats with SCI, providing a potential alternative treatment for
spinal cord injuries.
Key words
gait, GnRH agonist, locomotion, spinal cord
C1-04
MODULATION OF INFLAMMATORY RESPONSES BY SO-
LUBLE TNF RECEPTOR IN A RAT MODEL OF CERVICAL
SPINAL CORD INJURY (SCI)
Pan, J.Z., Singhal, N.S., Chang, Y.W., Lee, S.M., Huie, J.R., Lin, A.,
Sacramento, J., Ferguson, A.R., Bresnahan, J.C., Beattie, M.S.
Brain and Spinal Injury Center, Dept. of Neurological Surgery,
UCSF, SF, USA
Initial mechanical damage to the spinal cord induces acute inflam-
matory responses that contribute to secondary injury and cell death,
thus impairing functional recovery. Following SCI, TNFa initiates
downstream inflammatory cascades and is a key mediator of ex-
citotoxic injury by increasing synaptic calcium-permeable AMPA
receptor expression. Previous work in our lab has shown intrathecal
delivery of sTNFR1 can significantly improve behavioral outcome
and reduce microglial activation at the injury site during 6 week
evaluation. The goal of the current study is to investigate the mech-
anisms through which intrathecal sTNFR1 mediates inflammatory
responses and helps to improve function following SCI.
Long-Evans female rats (n = 52) received intrathecal delivery of
350 ng sTNFR1 90 minutes following unilateral C5 contusion injury
(75 kdyne) or C5 laminectomy without injury. Animals were sacri-
ficed at 3 h, 24 h or 7 d after injury. In two groups, spinal cord, serum
and spleen samples were harvested and analyzed for inflammatory
markers by Luminex multiplex assay or quantitative PCR. In other
groups, animals were used for spinal cord histological assessment and
flow cytometric analysis of peripheral leukocytes. Early after SCI,
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