30 / 162
number was significantly higher, 2.07
–
0.19 (P
<
0.0001) and
2.37
–
0.42 (P
<
0.001), respectively. Following focal impact TBI, rel-
ative mtDNA copy number was also significantly higher, 1.35
–
0.12
(P
<
0.0001) at 25 hours. Alterations in mitochondrial respiration in the
hippocampus and cortex performed post-TBI correlated with changes in
peripheral blood relative mtDNA copy number. Our data suggests that
isolated TBI stimulates the peripheral innate immune response, likely
stimulating mitochondrial biogenesis of leukocytes and circulating free-
extracellular mtDNA. In addition, alterations in peripheral blood rela-
tive mtDNA copy numbers may be a novel biosignature of cerebral
mitochondrial bioenergetics with exciting translational potential for
non-invasive diagnostic and interventional studies.
Keywords: Pediatric traumatic brain injury, Mitochondria, mito-
chondrial DNA, Biomarker, Cerebral Bioenergetics, Blood
A5-03
ALTERATIONS OF CIRCULATING CHEMOKINES IN RELA-
TION TO NEUROLOGICAL OUTCOME AFTER MODERATE-
TO-SEVERE TRAUMATIC BRAIN INJURY
Shawn Rhind
2
, A.P. Di Battista
1,2
, M. Hutchison
1
, A.J. Baker
1,3
, M.Y.
Shiu
2
, A. Capone-Neto
2
, S.B. Rizoli
1,2
1
University of Toronto, Institute of Medical Science, Toronto, Canada
2
Toronto Research Centre, Defence Research & Development Cana-
da, Toronto, Canada
3
University of Toronto, Depts. of Critical Care, Anesthesia & Surgery,
Toronto, Canada
Background:
Migration of peripheral inflammatory cells into the central
nervous system (CNS) is known to contribute to secondary injury
mechanisms after traumatic brain injury (TBI). Cellular activation and
infiltration of leukocytes into the brain is orchestrated by changes in the
expression of chemokines and their receptors; this process may initiate
CNS repair after trauma, but can also exacerbate injury via disruption of
the blood-brain barrier and induction of vasogenic edema, with adverse
consequences on patient outcome. Thus, evaluation of circulating che-
mokine profiles early post-injury may further our understanding of their
role in TBI, and their relationship to patient outcome.
Purpose:
Using a multimarker approach to characterize changes in
blood chemokines in the acute period following moderate-to-severe
TBI, and in association with 6-month neurological outcome using the
extended Glasgow Outcome Scale.
Methods:
Peripheral blood was drawn from 181 TBI patients
(
N
=
138 severe,
N
=
43 moderate) on admission, 6-, 12-, 24-h post-
injury; matching control samples were collected from healthy vol-
unteers (
N
=
21). Plasma concentrations (pg/mL) of eotaxin, eotaxin-3,
interferon-inducible protein (IP)-10, interleukin (IL)-8, monocyte
chemotactic protein (MCP)-1,
-
4, macrophage derived chemokine
(MDC), macrophage inflammatory protein (MIP)-1
b
, and thymus-and
activation-regulated chemokine (TARC), were quantified using a
high-density, ultra-sensitive MULTI-ARRAY immunoassay.
Results:
Significant increases in all chemokines assayed were ob-
served over the 24 h sampling period in patients, with the exception of
eotaxin-1, which was not altered, and both MDC and IP-10, which
were reduced relative to controls. Elevated admission levels of IL-8,
MCP1, MIP-1
b
and eotaxin-1 were associated with poor 6-month
neurological outcome, while altered levels of 7 of 9 assayed chemo-
kines were associated with mortality.
Conclusion:
TBI patients display altered systemic chemokine
profiles. These alterations are associated with negative patient out-
come at 6-months and support potential roles in modulation of neu-
roinflammation and neuroregeneration after TBI.
Keywords: neuroinflammation, IL-8, MCP1, MIP-1
b
, eotaxin-1
A5-04
NEURON-SPECIFIC ENOLASE IS SIGNIFICANTLY COR-
RELATED TO OUTCOME POST TRAUMATIC BRAIN IN-
JURY, ALBEIT NOT IN PRESENCE OF SERUM S100B
Eric Thelin
1
, Emma Jeppsson
1
, David Nelson
2
, Stefania Mondello
3
,
Mikael Svensson
1
, Bo-Michael Bellander
1
1
Karolinska Institutet, Clinical Neuroscience, Division of Neurosur-
gery, Stockholm, Sweden
2
Karolinska Institutet, Physiology and Pharmacology, Division of
Anesthesiology and Intensive Care, Stockholm, Sweden
3
University of Messina, Department of Neurosciences, Messina, Italy
Background:
Neuron-specific enolase (NSE) and S100B are bio-
markers of different cellular origin that mirror distinct types of injury
and pathophysiological mechanisms in TBI. The aim of this study was
to determine NSE correlation to cerebral injury and towards outcome
in models with, and without, S100B.
Materials and Methods:
A total of 340 TBI patients admitted to the
neuro-intensive care unit at Karolinska University Hospital, from 2005–
2011 were included. Serum S100B and NSE were measured in a first
sample obtained within 48h, and in additional two samples obtained within
72h after trauma. Clinical data were acquired from hospital charts. Glas-
gow outcome score (GOS) was evaluated 3 months after trauma. Re-
gression analyses were performed to examine associations between
biomarkers and injury severity and outcome. The pseudo-R
2
(i.e., the
percentage variance in outcome explained by the variables) was calculated.
Results:
Peak NSE and S100B serum levels were correlated
(r
=
0.61, p
<
0.0001). In univariate analyses, NSE levels were not cor-
related to the cerebral injury on CT scans, while S100B levels was
(Stockholm CT-score, p
=
0.0014). Biomarker levels sampled later after
trauma yielded more accurate outcome prediction than the initial levels
(NSE, 1st sample pseudo-R
2
=
0.8% vs. 3rd sample 7.7%; S100B, 1st
4.8% vs. 3rd 17.6%). Models including age, Glasgow coma scale, pupil
responsiveness, injury severity score, Stockholm CT-score and S100B
presented a pseudo-R
2
of 37.3%, while the same model including NSE,
instead of S100B, yielded only 33.3%. NSE did not have an additional
contribution when was used in the S100B-model (p
=
0.8).
Conclusion:
Serum levels of NSE are correlated to outcome with
an increasing predictive capability in later samples. However, NSE
did not correlate with injury severity as assessed by CT; neither does it
provide any additional information in the presence of S100B.
Keywords: Biomarkers, Traumatic brain injury, Outcome predic-
tion, NSE, S100B
A5-05
TRANSCRANIAL DOPPLER MEASURES EFFECTS OF MIND-
BODY TRAINING ON CEREBRAL AUTOREGULATION IN
SERVICE MEMBERS WITH COMBAT RELATED TBI
Ling Wong
1,2
, Kathy Williams
1
, Alex Razumovsky
3
, Michael
Dretsch
1
, Geoffrey Grammer
1
, Donna Neuges
1
, Thomas DeGraba
1
1
National Intrepid Center of Excellence, Bethesda, USA
2
Cherokee Nation Technology Solutions, Catoosa, USA
3
Sentient Neurocare, Hunt Valley, USA
Background:
Disruption of the autonomic nervous system, including
cerebral vasoreactivity (CVR), has been observed following acute
traumatic brain injury (TBI) and may also be associated with chronic
TBI symptoms. In chronic mild TBI (avg 2.3 years), we recently
reported that over 40% of service members (SM) exhibited abnormal
cerebral vasodilatory response to CO
2
during breath holding index
(BHI) using Transcranial Doppler (TCD). To address this
A-30