NNS 2015 Abstract Book

Oregon Health & Science University, Emergency Medicine, Port-

land, USA

Oregon Health & Science University, Immunology, Portland, USA

Oregon Health & Science University, Surgery, Portland, USA

Introduction:

Up-regulation of aseptic inflammation is a prominent

feature of major trauma and may contribute to early fever. Observa-

tional studies in traumatic brain injury (TBI) linking fever with poor

outcome often lack control groups with major trauma. We hypothe-

sized that patients with TBI would display a higher incidence of early,

presumably neurogenic, fever than patients with major trauma (MT)

without brain injury.

Methods:

We prospectively enrolled patients with MT with and

without TBI from a busy level I trauma center ICU. MT was defined

as injuries sufficient to warrant ICU admission, without head injury.

TBI was defined as admission Glasgow Coma Score (GCS)

13 not

related to intoxication or hemorrhagic shock, or the presence of

intracranial hemorrhage on admission CT scan. Severe TBI was

defined as GCS 3–8. Hourly temperatures were recorded in both

groups for the first 48 hours of hospitalization. Early fever was de-

fined at least one recorded temperature of

38.4 C in the first 48

hours after admission.

Results:

Data from the first consecutive 200 subjects of this on-

going trial were analyzed. About half of the cohort met criteria for

TBI (n

99). Injury Severity Score (ISS) was higher in the TBI group

(22 [17–29] v. 17 [10–26], P

0.01). Early fever was equally common

between the TBI (16%) and major trauma (16%). When analyzing the

group as a whole, controlling for culture verified infection, ISS, Head

Abbreviated Injury score (HAIS), the odds of developing early fever

was 13% (95% CI 2% to 41%) higher with each point decrease in

GCS. Repeating the regression model in only the TBI patients, the

odds of developing early fever was 20% (95% CI 2 to 41%) higher

with each point decrease in GCS and 75% (95% CI 22% to 92%)

higher with each point increase in HAIS.

Conclusion:

While the incidence of early fever is similar among

critically injured trauma patients, early fever may signify more severe

brain injury in TBI. Future work will better characterize the rela-

tionship between early fever and aseptic inflammation, which may

potentiate secondary brain injury.

Keywords: fever, inflammation, secondary brain injury

C7-11

GREY AND WHITE MATTER PATHOBIOLOGY OF A

NEWLY DEVELOPED MODEL OF CHRONIC REPETITIVE

CONCUSSIVE HEAD INJURY

Joseph Ojo

, Benoit Mouzon, Corbin Bachmeier, Moustafa Algamal,

Paige Leary, Cillian Lynch, Michael Mullan, Fiona Crawford

Roskamp Institute, Neuroscience, Sarasota, USA

Accumulation of repetitive concussive head injury experienced over

the careers of professional athletes in sports, such as, boxing and

American football is a major risk factor for the development of

neurodegenerative diseases in later life.

We have developed a new mouse model paradigm to explore the

risk of repetitive concussive head injury over a prolonged period of

time, and the age-associated post-injury factor on neuropathological

outcome.

Briefly this new closed head injury model involves delivering two

concussive head injuries on a weekly basis, with a minimum inter-

injury interval of 48 hours, repeated over 3 to 4 months. Animals were

euthanized between 2 to 3 months post last injury.

To characterize and validate our model we have chosen to explore a

host of relevant pathological markers. These markers include: dif-

ferent tau species, neurofilament H (NFL-H),

-synuclein, TAR-

DNA-binding protein 43 (TDP-43), neuroglial markers (GFAP, IBA-

1, CD45, vimentin), inflammatory cytokines (IL-1

, TNF

, IL-6,

1L-4, 1L-10), axonal markers (MBP, APP, Luxol fast blue, silver

staining) and lipid species. We correlate these pathological and bio-

chemical profiles with neurobehavioral outcome in tests that examine

sensorimotor performance (open field), anxiety (elevated plus maze),

social interaction/memory (3-chamber test) and cerebral blood flow

(laser Doppler imager). Our data thus far shows a significant dramatic

increase in neuroglial markers in injured animals compared with

shams. Axonal integrity was significantly altered in injured animals at

chronic timepoints post-injury. No significant changes were observed

-synuclein or TDP-43. A reduction in total tau (tau46) levels was

observed in correlation with an apparent increase in tau oligomer level

(TOC-1). Other biochemical and behavioral analyses are currently

ongoing in this model. This model could be useful in examining

chronic effects of repetitive concussion over-life span of individuals

involved in sport.

This study is funded by the Roskamp Foundation.

Keywords: hTau mice, repetitive concussions, ageing, biochemical

profiles, neurodegeneration

C7-12

COMBINED HEAD INJURY PLUS RADIATION EXPOSURE

SHIFTS SYSTEMIC RESPONSE TO IRRADIATION FROM

ANTI- TO PRO-INFLAMMATORY

Hulya Bayir

, Emin Fidan

, Michael Epperly

, Jesse Lewis

, Valerian

Kagan

, Joel Greenberger

Safar Center for Resuscitation Research, Critical Care Medicine,

Pittsburgh, USA

University of Pittsburg, Radiation Oncology, Pittsburgh, USA

University of Pittsburgh, Environmental & Occupational Health,

Pittsburgh, USA

A subpopulation of victims of a nuclear fission device may sustain

both ionizing radiation and traumatic brain injury. Despite advances in

the understanding of pathophysiology of whole body irradiation

(WBI), little is known about the mechanisms of damage after com-

bined WBI and head injury. Here we developed a combined WBI plus

traumatic brain injury model and tested the hypothesis that combined

injury will enhance systemic and cerebral inflammatory response vs.

either injury alone. Eleven week old C57BL/6NTac male mice were

divided into 4 groups: naı¨ve, WBI only (9.1 Gy), controlled cortical

impact (CCI) only and combined WBI

CCI. Mice were sacrificed at

24h or 40d after injury. Levels of thirteen cytokines, six chemokines,

and three growth factors were measured in serum and in three brain

regions (cortex, hippocampus and striatum). 24h serum levels of IL-6,

KC, and G-CSF were higher after WBI

CCI vs. either injury alone.

Irradiation specifically increased serum IL-10 levels at 24h vs. naı¨ve,

CCI and WBI

CCI. By 40 days levels of inflammatory mediators

normalized in the serum. The effect of irradiation on the brain was

primarily seen in the hippocampus with increases in IL-5, IL-7, IL-15,

TNF-

, Rantes and MIP-2 at 24 h. The effects of CCI and WBI

CCI

on cerebral inflammatory mediators were similar and observed in all

three brain regions tested with robust increases in G-CSF, IL-6, TNF-

KC, IP-10, MCP-1, Rantes, MIP-1

and MIP-2 at 24 h. Only IP-10

and Rantes remained elevated in striatum at 40d after WBI

CCI

while tissue cytokine levels normalized by 40d after WBI or CCI

alone. Combined injury enhanced acute systemic pro-inflammatory

A-90