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of ROS can preserve vascular function and lead to improved out-
comes. We tested the antioxidant Dendro[60]fullerene (DF-1) to de-
termine if reducing ROS levels would improve outcomes after TBI.
Methods:
For all experiments, male Sprague-Dawley rats received
either sham, moderate fluid percussion TBI alone or TBI followed by
treatment with DF-1 (10 mg/kg, i.v.) one hour post-injury. For ex-
periments to determine DF-1’s effects on the vasodilatory responses,
middle cerebral arteries (MCA) were harvested two hours after injury.
The MCA’s response to reduced intravascular pressure was assessed
by measuring MCA diameters after incremental decreases in pressure
from 100 to 20 mmHg. For FluoroJade C (FJC) experiments, animals
were euthanized 24 hours after injury. Brains were harvested, stained
and the numbers of FJC positive neurons in the hippocampus were
counted. In a third group of animals, beam balance and beam walk
testing was done on days 0 to 4 and Morris water maze (MWM)
testing was completed on days 11 to 15 after injury.
Results:
MCA vasodilatory responses were not significantly im-
proved by DF-1. In contrast, the total number of FJC positive cells
were significantly decreased with DF-1 treatment. DF- 1 treatment
also significantly (p
<
0.05 vs TBI alone) improved performance in the
MWM and beam walk tasks. DF-1 treatment did not significantly
improve beam balance performance.
Discussion:
Our results that DF-1 does not improve the cerebral
vasodilatory response are consistent with our previous physiological
studies of MAP, CVR and cerebral perfusion. However, DF-1 did
reduce neuronal cell death in the hippocampus and improve outcome
in behavioral testing. Since carboxyl-functionalized fullerenes such as
DF-1 cross the blood brain barrier, their neuroprotective properties
may be related to antioxidant actions within the brain parenchyma.
Keywords: Nanotechnology
D9-07
PERIPHERAL BLOOD MARKERS OF VASCULAR INJURY
IN MODERATE-TO-SEVERE TBI - RELATIONSHIP TO
SYSTEMIC CATECHOLAMINES AND OUTCOME
Alex Di Battista
1,2
, Shawn Rhind
2
, Andrew Baker
1,3
, Shiu Maria
2
,
Michael Hutchison
4
, Antonio Capone-Neto
3
, Sandro Rizoli
3
1
University of Toronto, IMS, Toronto, Canada
2
Defence Research & Development, Immunology, Toronto, Canada
3
University of Toronto, Depts of Critical Care, Anesthesia & Surgery,
Toronto, Canada
4
University of Toronto, FKPE, Toronto, Canada
Background:
Traumatic brain injury (TBI) causes damage to the
neurovascular unit, resulting in the release of associated molecules
that cross the disrupted blood-brain barrier into the systemic circu-
lation. Additionally, sympathetic activation accompanying TBI may
exacerbate endothelial damage. However, few clinical studies have
assessed vascular injury molecules in relation to catecholamines and
neurological outcome after TBI.
Purpose:
To evaluate a panel of soluble endothelial activation/
injury molecules in moderate-to-severe TBI patients; determine pos-
sible associations of these markers with circulating catecholamine
levels and 6-month neurological outcome assessed by extended
Glasgow Outcome Scale (GOSE).
Methods:
Peripheral blood was drawn from 181 TBI patients
(N
=
138 severe, N
=
43 moderate) on admission, 6-, 12-, and 24-h
post-injury; control samples were collected from healthy volunteers
(N
=
21). Plasma concentrations of endothelial-selectin (E-selectin),
platelet selectin (P-selectin), c-reactive protein (CRP), serum amy-
loid-A (SAA), thrombomodulin (TM), intercellular adhesion molecule
(ICAM)
-
1,
-
3, and vascular cell adhesion molecule (VCAM)-1, were
quantified using a ultra-sensitive MULTI-ARRAY immunoassay.
Plasma epinephrine (Epi) and norepinephrine (NE) levels were eval-
uated by ELISA.
Results:
Within 24 h of admission, TBI patients showed significant
differences in concentrations of all vascular injury molecules com-
pared to controls, with the exception of TM. At admission only P-
selectin differed from controls. Differences between moderate and
severe TBI were observed in E-selectin and ICAM-3. High admission
catecholamine values were associated with alterations in TM, P-se-
lectin, ICAM-1, CRP and SAA. Elevated levels of TM and P-selectin
were associated with unfavorable 6-month outcome and mortality;
mortality was also associated with elevated admission levels of
ICAM-1.
Conclusion:
Moderate-to-severe TBI is characterized by alterations
of plasma vascular injury/activation biomarkers. These markers are
associated with poor outcome at 6-months and may be mediated by
enhanced sympathetic activation.
Keywords: TBI, Vascular Injury, outcome, catecholamines
D9-08
FUNCTIONAL NEAR INFRARED SPECTROSCOPY (FNIRS)- 2
NON-INVASIVE METHODS TO ASSESS TRAUMATIC VAS-
CULAR INJURY AFTER TBI
Franck Amyot
1
,
Kimbra Kenney
1
, Victor Chernomordik
2
, L Christine
Turtzo
3
, Leah Harburg
1
, Carol Moore
1
, Emily Spessert
1
, Erika
Silverman
1
, Ramon Diaz-Arrastia
1
1
USUHS, Neurology, Bethesda, USA
2
NIH, NICHD, Bethesda, USA
3
NIH, NINDS, Bethesda, USA
Objective:
Assess 2 methods, fNIRS with hypercapnia (NIRS-CO
2
)
and cognitive (NIRS-COG) challenges, of cerebrovascular reactivity
(CVR) among healthy control (HC) and traumatic brain injury (TBI)
subjects.
Background:
Injury to cerebral blood microvessels is a well-rec-
ognized consequence of TBI. Functional Near-InfraRed Spectroscopy
(fNIRS) can non-invasively measure changes in oxyHb concentration.
It is less expensive and easier to use in outpatient settings than MRI-
based technologies.
Design/Methods:
We devised two fNIRS testing paradigms- NIRS
partnered with frontal lobe activation and hypercapnia challenges. We
tested 22 TBI subjects, and 15 age/gender-matched HC with NIRS-
CO
2
and MRI-BOLD with hypercapnia challenge. We also tested 32
TBI and 15 HC with NIRS-COG and abbreviated neuropsychological
testing. In both NIRS-CO
2
and MRI-BOLD, hypercapnia was induced
with a Douglas bag fitted with a valve that supplied room air alter-
nating each minute with room air mixed with 5% carbon dioxide
(CO
2
). CVR was calculated as a percentage of change in the blood
concentration (NIRS-CO
2
) or MRI-BOLD signal divided by the var-
iation of EtCO
2
(CVR
=
D
Hb /
D
EtCO
2
or%
D
BOLD signal/
D
EtCO
2
).
With NIRS-COG, we measured the changes in regional blood con-
centration between two different cognitive loads.
Results:
TBI subjects have lower and more variable CVR values
than HC (NIRS-CO
2
: TBI mean 0.293
–
0.039; HC, mean
0.336
–
0.014; p
=
0.0085) and correlates with neuropsychological
testing. Global CVR measured with BOLD fMRI is highly correlated
with CVR in frontal regions measured by NIRS-CO
2
(R
2
=
0.68). For
NIRS-COG measurement, TBI have a higher blood volume ratio than
HC (NIRS-COG: TBI mean 1.35; HC mean 1.18, p
=
0.027).
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