NNS 2015 Abstract Book

caspase-3 mRNA expression was measured by qRT-PCR in laser-

captured cortical neurons. Microglia activation and neuronal injury

was assessed in brain sections by immunofluorescence using specific

antibodies against CD11b and activated caspase-3 respectively.

Results:

In the vestibulomotor and cognitive tests, SPL-treated

animals performed significantly better than the BINT group and

similarly to SHAM animals (one-way ANOVA,

0.05). SPLT up-

regulated mRNA encoding BDNF and down-regulated the pro-apo-

ptotic protein caspase-3 in cortical neurons (one-way ANOVA,

0.05). Immunofluorescence demonstrated that SPLT inhibited

microglia activation and reduced the number of cortical neurons ex-

pressing the activated form of caspase-3 (one-way ANOVA,

0.05).

Conclusions:

These data strongly support the neuroprotective ef-

fect of SPLT and it prompts further studies aimed at developing SPLT

as a therapeutic intervention 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: Pulsed Laser Therapy, Neurotrauma, Ultrasound,

Traumatic Brain Injury

D8-22

FUNCTIONAL PRESERVATION OF RETINAL GANGLION

CELLS WITH P7C3-S243 FOLLOWING BLAST MEDIATED

TBI

Matthew Harper

, Terry Yin

, Laura Dutca

, Danielle Rudd

Andrew Pieper

VA Health Care System; University of Iowa, Department of Oph-

thalmology and Visual Sciences, Iowa City, USA

VA Health Care System; University of Iowa, Department of Psy-

chiatry, Iowa City, USA

Traumatic brain injury (TBI) frequently leads to chronic visual

dysfunction. The goal of this study was to evaluate potential

neuroprotection of retinal ganglion cell (RGC) function by the

neuroprotective molecule P7C3-S243 after blast-mediated TBI.

Blast-mediated TBI was modeled using an enclosed blast chamber

to generate a blast wave. Analysis of RGC function was performed

using the neutral position and provocative pattern electro-

retinogram (PERG) 1, 4 and 16 weeks post injury. Decrements in

neutral position PERG after blast-mediated TBI occur in a tem-

porally bimodal fashion, with a temporary recovery 4 weeks after

injury followed by chronically persistent dysfunction 16 weeks

following induction of injury. However, analysis of the provocative

PERG demonstrated a decreased amplitude 4 weeks post injury.

Taken together these results indicates persistent sub-clinical RGC

dysfunction. We have also shown that treatment with P7C3-S243

prevented a decrease in the provocative PERG 4 weeks post injury.

Chronic treatment with P7C3-S243 also prevented chronic changes

in the PERG 16 weeks post injury. These results suggest that

provocative PERG testing may serve as a noninvasive test in the

living organism to identify early damage to the visual system, and

may also reflect corresponding damage in the brain that is not

otherwise easily detectable. These findings might provide the basis

for developing an earlier diagnostic test to identify patients at risk

for developing chronic visual dysfunction after TBI at an earlier

stage when treatments may be more effective in preventing chronic

dysfunction. In addition, we have shown tht treatment with the

neuroprotective agent P7C3-S243 after TBI protects the visual

system dysfunction after TBI.

Keywords: Retina, Vision, Ganglion Cell, electroretinography

D8-23

EVALUATION OF KOLLIDON VA64 IN THE WRAIR PBBI

MODEL: STUDIES FROM THE OPERATION BRAIN TRAU-

MA THERAPY (OBTT) CONSORTIUM

Krista Caudle

, Stefania Mondello

, Janice Gilsdorf

, Frank

Tortella

, Deborah Shear

Walter Reed Army Institute of Research, Brain Trauma Neuropro-

tection and Neurorestoration, Silver Spring, USA

University of Messina, Neurosciences Department, Messina, Italy

Operation Brain Trauma Therapy (OBTT) is a multi-center con-

sortium established to provide cross-model preclinical screening of

emerging traumatic brain injury (TBI) therapies. Kollidon VA64, the

drug selected for testing by the OBTT, is a novel agent that has

demonstrated cell membrane-resealing properties that decrease TBI

induced blood brain barrier permeability as well as cytotoxic and

traumatic brain edema in both

in-vitro

and

in-vivo

TBI models.

Using the standard OBTT protocol, we assessed therapeutic efficacy

of Kollidon VA64 on neurobehavioral and neuropathological out-

comes in the WRAIR PBBI model of severe TBI. Unilateral frontal

PBBI was produced in the right hemisphere of isoflurane anesthe-

tized rats (10% injury severity level). Low (0.2 g/5 mL) or high

(0.4 g/5 mL) doses of VA64 were administered as a single intrave-

nous (IV) infusion 15 m post-injury. Motor and cognitive testing was

conducted using the rotarod at 7 and 10 days, and Morris water maze

(MWM) from 13–17 days post-PBBI, respectively. Rotarod testing

revealed similar deficits across all injury groups with mean latencies

reduced by 51

–

7% (vehicle), 46

–

9% (low), and 48

–

9% (high) vs.

sham; however no significant improvement in motor outcome was

detected across animals treated with VA64. MWM results revealed

significant deficits in all injury groups with the average latency to

find the hidden platform (across testing days) increased by 85

–

16%

(vehicle), 123

–

21% (low), and 106

–

18% (high) vs. sham. Al-

though no significant therapeutic effect was detected on spatial

learning for MWM acquisition trials, intermediate beneficial effects

were observed on the probe (missing platform) trials and thigmo-

taxis testing where animals treated with the high dose

did not

differ

from sham. Overall, the results of the current study indicate that a

single post-injury infusion of VA64 conferred only very modest

cognitive benefit in the PBBI model. Histology and biomarker re-

sults are pending. Supported by U.S. Army Grant W81XWH-10-1-

0623.

Keywords: traumatic brain injury (TBI), Kollidon VA64, Operation

Brain Trauma Therapy (OBTT), neurobehavior motor cognitive

D8-24

THE EFFECTS OF SLEEP-ALTERING DRUGS ON SLEEP

ARCHITECTURE RELATIVE TO TRAUMATIC BRAIN IN-

JURY IN RATS

Andrea Mountney

, Deborah Shear

, Chanyang Rho

, William

Flerlage

, Jacqueline Dougherty

, Kara Schmid

, Thomas Balkin

Frank Tortella

Walter Reed Army Institute of Research, BTNN, Silver Spring, USA

Walter Reed Army Institute of Research, Behavioral Biology, Silver

Spring, USA

Service members often rely on sleep-altering drugs (caffeine/zolpi-

dem) to counteract the effects of sleep-loss and/or insomnia. However,

their impact on traumatic brain injury (TBI) recovery is unknown.

This study aimed to (1) determine the effects of caffeine/zolpidem on

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