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survival by preserving more NeuN positive cells than in control rats. Such

neuroprotective effects were blocked by co-treatment with GDNF neu-

tralizing antibody. Western blot analyses revealed that rat brains with

hNSC transplantation expressed higher levels of GDNF receptors, as well

as phosphorylated ERK, AKT and GSK3

b

-S9. In summary, our results

demonstrate that hNSC grafts have a beneficial effect on neuronal survival

in rat hippocampi after TBI plus hemorrhage, and the underlying mecha-

nism of this neuronal protection is at least partially due to GDNF-mediated

modulation of the key survival signaling pathways.

Keywords: traumatic brain injury, GDNF, neural stem cell, hip-

pocampus, signal pathway

A2-15

ACUTE EFFECTS OF 17ß-ESTRADIOL ON OXIDATIVE

STRESS RESPONSE PROTEINS AFTER TBI

Jutatip Guptarak

, Ya Ping Zeng, Maria-Adelaide Micci, Helen

Hellmich, Douglas DeWitt, Stacy Sell

University of Texas Medical Branch, Anesthesiology, Galveston, USA

Background:

Traumatic brain injury (TBI) induces secondary cellu-

lar damage mediated in part by reactive oxygen species that initiate

oxidative stress responses in neuronal and cerebrovascular tissue. The

expression of oxidative stress response genes is altered in both hip-

pocampus and cerebrovasculature by TBI and is partially restored by

acute treatment with 17

b

-estradiol (E

2

). Additionally, TBI alters the

expression of cerebrovascular gap junction proteins (connexins). Here

we investigate the effect of E

2

treatment after TBI on connexin pro-

teins and selected protein products of oxidative stress response genes.

Methods:

Ovariectomized female rats received moderate fluid-

percussion or sham injury followed 15 min later by vehicle (Veh, 1 ml/

kg, s.c.) or E

2

(33

l

g/kg, s.c.), providing three treatment groups

(Sham

+

Veh, TBI

+

Veh, or TBI

+

E

2

). Brains were harvested 15 min

after treatment and fresh frozen. Cerebral blood vessels were isolated

and total proteins extracted. Western blot analysis was performed

using antibodies against uncoupling protein 3 (UCP3), glutathione

peroxidase 2 (GPX2), and connexin 43 (Cx43).

Results:

One-way ANOVA followed by Tukey’s HSD test showed

an overall effect of treatment on UCP3 protein (F

(2,8)

=

21.191,

P

=

0.002) with significant differences between all three treatment

groups. TBI significantly reduced UCP3 protein level (

P

=

0.002). E

2

treatment increased UCP3 protein level (

P

=

0.042) but not to the same

level as the Sham

+

Veh group (

P

=

0.038). There were no significant

differences in GPX2 and Cx43 protein levels.

Conclusions:

Uncoupling proteins are mitochondrial inner mem-

brane anion carriers involved in the electrochemical gradient across

the mitochondrial membrane and mitochondrial production of reactive

oxygen species. Since estrogens are known to regulate mitochondrial

proteins; our data suggest that UCP3 may be a mediator of the pro-

tective effects of E

2

on cerebral blood vessels after TBI.

Support:

These studies were completed as part of an interdisci-

plinary research team funded by The Moody Project for Translational

Traumatic Brain Injury.

Keywords: estrogen, oxidative stress response, traumatic brain in-

jury, cerebral vasculature

A2-16

CHARACTERIZATION OF BRAIN MATERIAL PROPERTIES

FOLLOWING BRAIN BLAST INJURY

Ahmed Alshareef

1

, Lee Gabler

1

, James Stone

2

, Matthew Panzer

1

1

University of Virginia, Center for Applied Biomechanics, Charlot-

tesville, USA

2

University of Virginia, Department of Radiology and Medical Ima-

ging, Charlottesville, USA

Improvised explosive devices (IEDs) have caused traumatic brain injury

(TBI) in approximately 360,000 soldiers over the past decade, many of

whom suffer from long-term neurological consequences when treatment

is delayed. A better understanding of the mechanical response of the

brain during and after these events may assist diagnosis and outcome of

bTBI in both clinical and battlefield scenarios. Diagnostic methods

using non-invasive stiffness techniques, such as field-deployable ultra-

sound, rely on detecting changes to the mechanical properties of brain

tissue after injury; however, these tools require

a priori

information on

mechanical changes to injured tissue. Moreover, changes to the brain

mechanical properties with a blast injury may be a) region-specific, b)

time-specific, and c) blast severity-specific. The goal of this study is to

characterize changes in the mechanical response of brain tissue fol-

lowing blast injury. Thirty adult, male Sprague-Dawley rats were ex-

posed to a primary blast wave at one of two levels of blast severity: low

(18–20 psi peak overpressure) or high (30–25 psi peak overpressure).

Sham animals that were anesthetized but not blasted were used as a

control. Animals were sacrificed at either 2 or 24 hours following in-

jury, whole brains were extracted, and mechanical indentation tests

were used to characterize stiffness at five locations: frontal cortex,

midbrain superior, midbrain aqueduct, midbrain inferior, and brainstem.

Significantly higher forces were measured in the midbrain inferior re-

gion in the blast high 24 hour when compared to sham group (

+

50%,

p

<

0.05). In addition, we observed lower forces in the brainstem region

(

-

43%, p

<

0.05) of the blast low 24 hour as compared to the sham

group. There were no significant changes in the 2 hour groups. The

results show a temporal, regionally dependent mechanical response—

stiffening in the blast high 24 hour, softening in blast low 24 hour—to

injury. The mechanical changes can serve as correlates to injury to

improve detection and diagnosis of bTBI.

Keywords: Blast TBI

A2-17

SPINAL CORD INJURY CAUSES DISTINCT ACUTE AND

CHRONIC PHASES IN THE TESTES AND BLOOD TESTES

BARRIER OF A SPRAGUE-DAWLEY RAT MODEL

Ryan Fortune

1

, David Loose

1

, Raymond Grill

2

, Christine Beeton

3

1

UTHealth GSBS, Cell and Regulatory Biology and the MD/PhD

Programs, Houston, USA

2

University of Mississippi Medical Center, Neurobiology and Anato-

mical Sciences, Jackson, USA

3

Baylor College of Medicine, Molecular Physiology and Biophysics,

Houston, USA

Spinal Cord Injury (SCI) has been shown to reduce fertility in human

and rodent males. We have previously shown that SCI causes a

sustained breakdown of the blood testis barrier. Increased inflam-

matory and oxidative conditions in this setting could lead to an

immunological infertility due to exposure to the fragile and antigenic

cells in the seminiferous tubules. RNA and metabolomics data from

these animals support this hypothesis. We have given Sprague-

Dawley rats a thoracic contusion SCI, with cohorts in both acute and

chronic time points. Acutely, we see time dependent increases in

inflammatory and oxidative markers and a massive decrease in

transcription of testosterone producing enzymes followed by a de-

crease in cell cycle regulators, indicating that sperm production is

highly disrupted only after the initial fallout of the injury is fully

realized. Chronically, we see maintenance of a low level of immune

activity and a new steady state different from both naı¨ve and sham

A-24