NNS 2015 Abstract Book

Additionally, treatment with guanabenz reduced deficits in motor and

vestibulomotor function, improved recognition memory, as well as,

spatial learning and memory ability. Subjects treated with guanabenz

also demonstrated better cognitive flexibility relative to their vehicle

treated counter-parts. Intriguingly, delaying the start of treatment by

24 hours or reducing the dose to 0.5 mg/kg, resulted in many of the

same beneficial effects. Because of the persistent nature of cognitive

deficits following TBI there is a growing demand for effective treat-

ments. The results of the current study further lend support to ER

stress signaling being involved in TBI pathophysiology and that

guanabenz may aid in improving cognitive deficits.

Keywords: ER Stress, Hippocampus, Traumatic Brain Injury,

eIF2

, Learning and Memory, Recovery of Function

B7-07

EXPOSURE TO ANABOLIC ANDROGENIC STEROIDS DOES

NOT EXACERBATE ACUTE POST-INJURY OUTCOMES IN

MICE SUBJECTED TO REPETITIVE CONCUSSION

Dhananjay Namjoshi

, Michael Carr, Wei Hang Cheng, Kris Martens,

Shahab Zareyan, Anna Wilkinson, Cheryl Wellington

The University of British Columbia, Pathology and Laboratory

Medicine, Vancouver, Canada

Background:

An unknown proportion of athletes with high concus-

sion exposure develop chronic traumatic encephalopathy (CTE), a

neurodegenerative disease characterized by altered mood, behavior

and cognition, motor dysfunction and extensive deposition of phos-

phorylated tau. Factors that may modulate CTE risk are virtually

unknown. Androgenic anabolic steroids (AAS) are performance-

enhancing substances known to increase aggression and alter function

of the gonadal hypothalamic pituitary axis. Whether systemic expo-

sure of AAS increases the vulnerability of the brain to concussion is

not known. Here we tested the hypothesis that AAS treatment would

exacerbate aggression, neuroinflammation and/or tauopathy after re-

peated NFL-like concussion in mice.

Methods:

Gonadally-intact, 8-week old male C56Bl/6 mice were

treated with a cocktail of commonly used AAS (2.5 mg/kg each of:

17alpha-methyltestosterone, nandrolone and testosterone) or sesame

oil vehicle for 7 weeks prior to receiving two NFL-like concussions

spaced 24h apart using our previously described CHIMERA (Closed

Head Impact Model of Engineered Rotational Acceleration) model of

traumatic brain injury (TBI). Naı¨ve mice received neither AAS

cocktail nor sesame oil vehicle. Behavioral, biochemical and neuro-

pathological outcomes were assessed up to 7 days post-TBI.

Results:

Prior to repeated concussion, AAS-treated mice ex-

hibited increased body and seminal vesicle weights, reduced tes-

ticular weight, and reduced latency to fight in the resident-intruder

task of aggression. Compared to sham controls, mice subjected to

TBI were impaired in several behavioral measures including loss of

righting reflex, neurological severity score, accelerating rotarod

performance, and thigmotaxis. Naı¨ve and treated mice also dis-

played increased diffuse axonal pathology and white matter in-

flammation post-TBI. No significant treatment effect of AAS

exposure on TBI phenotypes was observed in any outcome measure

evaluated in this study.

Conclusions:

Under our experimental conditions, exposure of wild-

type male mice to AAS did not exacerbate any post-TBI outcome

including behavior, diffuse axonal injury, inflammation or phosphor-

ylation of murine tau.

Keywords: Chronic traumatic encephalopathy, Androgenic ana-

bolic steroids, Sport concussion

B7-08

EVIDENCE OF BOTH BRAIN AND SPINAL CORD INJURY

IN RATS EXPOSED TO EXPLOSIVE-DRIVEN PRIMARY

BLAST

Fabio Leonessa

, S. Krisztian Kovacs

, Erin Murphy

, Hongna Pan

John Magnuson

, Steve Parks

USUHS, Neurology, Bethesda, USA

Ora, Inc., Fredericksburg, USA

The high prevalence of blast-related brain injury among military ca-

sualties of recent wars has led to an increasing number of studies

focused on the vulnerability of brain to blast’s ‘‘primary’’ mechanism

of injury. Very little focus has been put on spinal cord’s vulnerability,

possibly because of lack of prominent specific symptoms. Balance

impairment is increased after exposure to primary blast, but is gen-

erally ascribed to vestibular injury. The objective of our study was to

evaluate the impact of primary blast on both brain and spinal cord.

The neurobehavioral and neuropathological outcome was evaluated at

several times following exposure of rats to explosive-driven primary

blast. After hearing loss, gait impairment, as objectively measured on

a Catwalk apparatus, represented the most significant behavioral

outcome of blast exposure, peaking at 15 days for several parameters.

The most prominent neuropathological feature was represented by

blast-intensity dependent FD Neurosilver- and Fluoro-Jade B-marked

neurodegeneration, evident between 7 and 28 days after exposure.

Areas of astrocyte and microglia activation coincided almost exclu-

sively with the areas of neurodegeneration. In brain, neurodegenera-

tion was detectable in the visual pathways, cerebellum and medial

lemniscus. Importantly, evidence of neurodegeneration was found at

all levels in the spinal cord. It involved dorsal corticospinal tract,

ventral and lateral funiculi, including the ventral medial fissure,

lamina 8 area of the ventral horns (all levels), and postsynaptic dorsal

column (cervical and thoracic levels). The second most prominent

pathological feature was the early (6 hours) raise of calpain-specific

alpha II spectrin breakdown products. This is possibly the first re-

ported evidence of spinal cord injury following live exposure of rats to

explosive-driven primary blast. While these data need to be verified,

in particular excluding a role for artifactual mechanisms mediated by

the blast exposure set-up, spinal cord injury should be kept into ac-

count in future studies on blast-related neurotrauma.

Keywords: Blast, Traumatic brain injury, Spinal Cord Injury

B7-09

A RAT MODEL OF UNDERBODY BLAST-INDUCED BRAIN

INJURY WITH EVIDENCE OF NEUROBEHAVIORAL DEFI-

CITS, NEURONAL DEATH AND INFLAMMATION

Flaubert Tchantchou

, Joshua Vaughan

, Parisa Rangghran

William Fourney

, Gary Fiskum

University of Maryland, Anesthesiology, Baltimore, USA

University of Maryland, Aerospace Engineering, College Park, USA

TBI resulting from exposure to explosive-blast targeting military

vehicles and their occupants is a major cause of casualties in the

recent wars in Iraq and Afghanistan. We developed a rat model of

under-vehicle, blast-induced-TBI that at low blast-intensity (50 G

force), displays histopathological evidence of diffuse axonal injury

and astrocytes activation, but no evidence of neuronal loss and be-

havioral deficits (Proctor et al., 2014). Here, we assess the impact of

increased blast-intensity on neuronal loss, inflammation, behavioral

impairments and lethality.

A-70