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A5-16
PROTON MAGNETIC RESONANCE SPECTROSCOPY PRE-
DICTORS OF TISSUE LOSS AFTER TRAUMATIC BRAIN
INJURY
Matthew Sharrock
1
, Hung-Wen Yeh
3
, William Brooks
1,2,4
, Janna
Harris
2,4
1
University of Kansas Medical Center, Neurology, Kansas City, USA
2
University of Kansas Medical Center, Anatomy and Cell Biology,
Kansas City, USA
3
University of Kansas Medical Center, Biostatistics, Kansas City,
USA
4
University of Kansas Medical Center, Hoglund Brain Imaging
Center, Kansas City, USA
Similar injuries among patients with traumatic brain injury (TBI) can
lead to a wide variety of pathological and clinical outcomes. Bio-
markers that predict injury progression could help elucidate mecha-
nisms of secondary injury and lead to strategies that mitigate their
effects. Experimental models of TBI have shown heterogeneity with
regards to tissue loss measured using T2-weighted MRI and histo-
pathology, despite the same initial parameters. An early neurochem-
ical profile of metabolic injury can be measured
in vivo
using proton
magnetic resonance spectroscopy (
1
H -MRS). Our goal was to de-
termine whether the spectroscopic profile of early TBI could predict
subsequent tissue loss.
We used a controlled cortical impact over the sensorimotor cortex
in adult male rats. High field
1
H-MRS was obtained from 1) a cortical
voxel proximal to the site of impact and 2) an underlying hippocampal
voxel at one hour (D0), one day (D1) and three days (D3) post injury.
We then obtained T2-weighted MRI at 14 days and measured the
amount of tissue loss by comparing the volume of preserved tissue in
the ipsilateral hemisphere versus the contralateral side. Statistical
significance was determined using correlation analysis.
We found significant correlations between several cortical and
hippocampal
1
H-MRS biomarkers and tissue loss at 14 days, however,
the predictive metabolic profiles varied between the two regions. The
strongest predictors in hippocampus were lactate on D0, aspartate on
D1 and n-acetyl aspartate on D3. The strongest predictors in cortex
were phosphocreatine on D1 and glucose on D3.
These results show that
1
H-MRS can predict injury progression, not
only when measured in visibly injured tissue but also in radiograph-
ically normal tissue adjacent to the injury site. If translated to human
use, these biomarkers could provide clinicians with predictors of in-
jury severity and targets for early intervention.
Keywords: Spectroscopy, TBI, CCI
A5-17
COMPARISON OF SYSTEMIC INFLAMMATORY PROFILES
IN HEALTHY ATHLETES WITH AND WITHOUT A HIS-
TORY OF CONCUSSION
Michael Hutchison
1
, Alex Di Battista
2,3
, Shawn Rhind
3,1
, Andrew
Baker
4,2
, Doug Richards
1
1
University of Toronto, Faculty of Kinesiology and Physical Educa-
tion, Toronto, Canada
2
University of Toronto, Institute of Medical Science, Toronto, Canada
3
Defence Research & Development Canada, Toronto Research Cen-
tre, Toronto, Canada
4
Departments of Critical Care, Anesthesia & Surgery, St. Michael’s
Hospital, Toronto, Canada
Background:
Chronic effects of concussion, a form of mild traumatic
brain injury (mTBI), are not well understood. The injury triggers
activation of central and peripheral immune cells with the infiltration
of neurological tissue and release of multiple inflammatory mediators.
It has also been hypothesized that a dysregulated immune response
may underlie the etiology of chronic health conditions. Therefore,
evaluating immune markers in the peripheral blood may provide
useful information reflecting brain immunopathology.
Objective:
To compare circulating profiles of inflammatory markers
in uninjured athletes with and without a history of concussion.
Methods:
Peripheral blood was sampled from 50 uninjured athletes
(
n
=
35 male;
n
=
15 female), stratified into two groups based on pre-
vious concussion history (
n
=
23 yes;
n
=
27 no). Relevant medical
history was obtained during pre-season by Sport Concussion Assess-
ment Tool 3. An ultra-sensitive MULTI-ARRAY immunoassay plat-
form was used to assess plasma concentrations (pg/ml) of 19 cytokines
(e.g., including: interleukin (IL)
-
6, tumor necrosis factor (TNF)
-
a
,
-
b
);
and 10 chemokines (e.g., macrophage inflammatory protein (MIP)
-
1
a
,
-
1
b
, monocyte chemoattractant protein (MCP)
-
1,
-
4, macrophage de-
rived chemokine (MDC), thymocyte- and activation-regulated chemo-
kine (TARC), and interferon gamma-induced protein (IP)
-
10).
Results:
Significant elevations of the cytokine IL-6 (p
=
0.003), and
the chemokines IP-10 (p
=
0.002) and MCP-4 (p
=
0.02), were ob-
served in healthy uninjured athletes with a history concussion com-
pared with those who had no previous concussions.
Conclusion:
Athletes with a history of concussion display an al-
tered systemic inflammatory profile compared to athletes with no
previous concussions. While chronic low-grade inflammation is gen-
erally considered a health detriment, the role of the inflammatory
response following concussive injury, with respect to long-term
neuroprotective or neurodegenerative effects remains unclear.
Keywords: Mild Traumatic Brain Injury, Concussion, Sport
A5-18
MULTIVARIATE BIOMARKER PROFILING, SENSORY
MOTOR DEFICITS, CONSCIOUSNESS AFTER SINGLE AND
REPEAT PROJECTILE CONCUSSIVE INJURY
Angela Boutte
, Andrea Mountney, Brittany Abbatiello, Shonnette Grant,
David Johnson, Casandra Cartagena, Frank Tortella, Deborah Shear
Walter Reed Army Institute of Research, Brain Trauma Neuropro-
tection and Neurorestoration Branch, Silver Spring, USA
Developing diagnostic and prognostic biomarkers for mild traumatic
brain injury (mTBI) has become an urgent medical need. The purpose
of this study was to evaluate and correlate the effects of single and
repeated mTBI on consciousness, sensory-motor deficits, and CSF
biomarker abundance. The projectile concussive impact (PCI) model
was used to induce mTBI. Anesthetized rats received single (1XPCI)
or repeated (2-4XPCI) impacts with 1h intervals. Matched controls
(sham) received anesthesia alone. Righting reflex (RR) was deter-
mined immediately; sensory-motor deficits (revised neurobehavioral
severity scale, NSS-R) were recorded after 45 min. CSF was collected
1h after the last impact and GFAP, UCH-L1, and Tau were analyzed
by ELISA. Key findings of average biomarker levels, behavioral
scores (p
£
0.05, vs. Sham) or correlations (p
£
0.05, Spearman
r
) are
reported. Results confirmed significant PCI-induced increases in RR
and composite NSS-R scores. Among individual NSS-R components,
1XPCI significantly increased drop and righting scores; only 4XPCI
increased the hind-paw sensory deficit. Levels of GFAP in CSF rose
to 5.47 ng/mL (1XPCI), 8.22 ng/mL (2xPCI), 2.97 ng/mL (3XPCI),
and 5.24 ng/mL (4XPCI). Tau was increased to 7.59 ng/mL (2XPCI)
A-35