2
Oregon Health & Science University, Emergency Medicine, Port-
land, USA
3
Oregon Health & Science University, Immunology, Portland, USA
4
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),
a
-synuclein, TAR-
DNA-binding protein 43 (TDP-43), neuroglial markers (GFAP, IBA-
1, CD45, vimentin), inflammatory cytokines (IL-1
b
, TNF
a
, 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
in
a
-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
1
, Emin Fidan
1
, Michael Epperly
2
, Jesse Lewis
1
, Valerian
Kagan
3
, Joel Greenberger
2
1
Safar Center for Resuscitation Research, Critical Care Medicine,
Pittsburgh, USA
2
University of Pittsburg, Radiation Oncology, Pittsburgh, USA
3
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-
a
, 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-
a
,
KC, IP-10, MCP-1, Rantes, MIP-1
b
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