‘polytrauma’ using Abbreviated Injury Scale (AIS) nomenclature
(head/neck
+
other body regions). Cerebrospinal fluid (CSF) IL-6 was
measured in samples collected 0-5d post-injury for 114 adults with
severe TBI. Group-based trajectory analysis (TRAJ) was conducted to
assess temporal IL-6 profiles. Injury type was compared to IL-6
TRAJ, which was used to predict 6 and 12 month Glasgow Outcome
Scale scores. There were two distinct CSF IL-6 profiles.
Group-1
had
an initial peak, followed by steady decline after d1;
Group-2
had a
sustained elevation. Injury type was associated with IL-6 TRAJ group
(
v
2
=
5.31, p
=
0.02). There was 70% concordance between those with
TBI
+
polytrauma and TRAJ
Group-1
; in contrast, isolated TBI was
nearly equally distributed between TRAJ subgroups. Compared to
TRAJ
Group-1,
individuals in
Group-2
had an increased odds of
unfavorable outcomes at 6 (OR
=
3.39, 95% CI: 1.25-9.18) and 12
months (OR
=
2.60, 95% CI: 1.02-6.64), after controlling for age and
GCS. We conclude the presence/absence of polytrauma is associated
with acute CSF IL-6 patterns. IL-6 TRAJ group classification sig-
nificantly predicted 1yr outcomes. Interestingly, polytrauma compli-
cating TBI shifted CSF IL-6 TRAJ from a sustained to a decelerating
profile. Future studies should explore additional factors contributing
to elevations in IL-6, and how to mitigate potentially detrimental
effects on outcome.
Support:
CDCR49-CCR323155;
DODW81XWH-071-0701;
NIH5P01NS030318.
Key words
inflammation, interleukin-6, polytrauma, traumatic brain injury
D1-13
HYPOTHERMIA AND
IN VITRO
HIGH-ENERGY TRAUMA
Cao, Y.
1
, Sko¨ld, M.K.
2
, Malm, E.
1
, Sonde´n, A.
3
, Risling, M.
1
1
Department of Neuroscience, Karolinska Institute, Stockholm, Swe-
den
2
Department of Neurosurgery, Uppsala University Hospital, Uppsala,
Sweden
3
Department of Clinical Science and Education, Section of Surgery,
Karolinska Institute, Stockholm, Sweden
Hypothermia (35 C) seems to have an impact on gene expression
post-trauma in the examined human neuroblastoma cell line. Com-
paring 35 C with 37 C post-trauma incubation - expression appeared
to be significantly different in 1428 genes.
To study hypothermia and high-energy trauma’s effects on human
neuroblastoma (SH-SY5Y) cells in absence of
in vivo
confounders,
such as the animals’ physiological thermoregulation.
In an
in vitro
model (the flyer-plate), a copper fragment becomes
accelerated by means of a laser. The fragment hits a cell-culture well
and causes high-energy trauma (shock-wave and cavitation) in a
neuroblastoma colony. Incubation prior to trauma was at 37 C for all
groups. An automatic equipment (CellIQ) incubated the colonies post-
trauma at 35 C and 37 C respectively. Pictures of the colonies were
taken every hour post-trauma by CellIQ. After 24 hr cells were har-
vested for gene array by Affymetrix procedures. Differential gene
expression (up- or down-regulation) was assessed with unpaired t-test.
The genes were functionally annotated using the Database for An-
notation, Visualization and Integrated Discovery.
Cutoff for differential expression was at least 200% up- or down
regulation, i.e. fold change (FC)
£
-2 and FC
‡
2, P
£
0.05. 1428 genes
were regulated 35 C-traumatised vs 37 C-traumatised: 518 down and
910 up between a FC-minimum at
-
4 and 20 folds maximum. 218
genes were regulated 35 C-traumatised vs 35 C-control: 77 down
(FC-min
= -
3), 141 up (FC-max
=
3). 1232 genes were regulated
35 C-control vs 37 C-control: 395 down (FC-min
= -
4) and 837 up
(FC-max
=
21).
Key words
automatic cell incubation, gene array microarray, gene expression
regulation, high energy
in vitro
trauma, human neuroblastoma cells
(SH-SY5Y), hypothermia, image-analysis, imaging
D1-14
MULTICENTER COMPARISON OF FIVE THERAPIES RE-
VEALS THERAPEUTIC POTENTIAL FOR LEVETIR-
ACETAM: OPERATION BRAIN TRAUMA THERAPY
Kochanek, P.M.
1,2
, Bramlett, H.
3
, Shear, D.
4
, Dixon, C.E.
1,2
, Dietrich,
W.D.
3
, Poloyac, S.
1,2
, Empey, P.E.
1,2
, Schmid, K.
4
, Mondello, S.
6
,
Wang, K.K.
5
, Hayes, R.
7
, Tortella, F.
4
1
Safar Center, Pittsburgh, USA
2
University of Pittsburgh, Pittsburgh, USA
3
University of Miami, Miami, USA
4
Walter Reed Army Institute of Research, Silver Spring, USA
5
University of Florida, Gainesville, USA
6
University of Messina, Messina, Italy
7
Banyan Biomarkers, Alachua, USA
Operation Brain Trauma Therapy (OBTT) is a multi-center pre-clin-
ical drug and biomarker screening consortium testing therapies for
TBI. OBTT utilizes the parasagittal fluid percussion injury (FPI),
controlled cortical impact (CCI), and penetrating ballistic-like brain
injury (PBBI) models in rats to screen therapies at three sites using
rigorous/blinded protocols. Identical groups (sham, TBI-vehicle, TBI-
low dose, and TBI-high dose) are used across sites and motor, cog-
nitive, histological, and serum biomarker outcomes assessed over
21 d. The code for each outcome is simultaneously broken across sites
and therapies are given an overall score (maximum
=
22 points/mod-
el). The first five therapies tested included nicotinamide (50 or 500
mg/kg IV at 15 min and 24 h), erythropoietin (EPO, 5000 or 10,000U/
kg IV at 15 min), cyclosporin-A (CsA, 10 or 20 mg/kg, IV at 15 min
and 24 h), simvastatin (1 or 5 mg/kg POX14 d), or levetiracetam (54
or 170 mg/kg IV at 15 min). Dosing was literature-based. The first
four therapies produced modest/no effects across models. Nicotina-
mide showed some motor benefit and tissue sparing in CCI, EPO
showed no benefit across models, CsA showed tissue sparing in FPI
but toxicity in CCI and PBBI, Simvastatin showed modest motor
benefit across models but no cognitive or histological benefit. Leve-
tiracetam, however, showed benefit on multiple outcomes including
on MWM and probe trial in FPI, motor function, MWM, and tissue
loss in CCI, and probe trial in PBBI. In OBTT, Levetiracetam, given
as a single IV bolus early post-TBI, shows promise. It merits explo-
ration of therapeutic window, dose optimization, testing in models
with second insults, and testing in our large animal model. Support:
US Army, W81XWH-10-1-0623
Key words
biomarker, consortium, pre-clinical, therapy
D1-15
PROTECTIVE EFFECTS OF PHENELZINE AGAINST
ALDEHYDE-INDUCED
EX VIVO
OXIDATIVE DAMAGE TO
CORTICAL MITOCHONDRIA
Cebak, J.E.
, Singh, I.N., Miller, D.M., Wang, J.A., Hall, E.D.
A-105
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