Page 42 - NNS 2014 Program & Abstract Book

Open Communications
OC1-01
HYPEROXIC VERSUS NORMOXIC RESUSCITATION IN A
RAT POLYTRAUMA MODEL OF TBI PLUS HEMORRHAGIC
SHOCK
Scutella, D., Pan, Y., Proctor, J.L., Fiskum, G.
University of Maryland Department of Anesthesiology, Baltimore,
USA
Many civilian and warfighter TBI victims experience additional injuries,
including those that result in hemorrhagic shock (HS). Reduced O2
delivery that accompanies HS may exacerbate TBI. This study tested the
hypothesis that inspiration of 100% O2 during resuscitation following
TBI and HS reduces brain lesion volume and improves neurologic
outcome compared to what occurs in the absence of supplemental O2.
Brain injury to isoflurane anesthetized adult male rats was induced
by controlled cortical impact (CCI) at a depth of 2.0 mm. HS was then
induced by extracting blood until the target range of 35–40 mm Hg for
mean arterial pressure was reached and maintained for 30 min. The
HS phase was followed by a one hr ‘‘Pre-Hospital’’ fluid resuscitation
phase utilizing infusion of Hextend. This period was followed by a
one hr ‘‘Hospital Phase’’ when shed blood was returned to rats. Rats
were randomized on the day of surgery to 4 groups with 10 rats per
group: A. Sham Normoxic. B. Sham Hyperoxic. C. Polytrauma
Normoxic. D. Polytrauma Hyperoxic. Normoxic animals inspired
room air and Hyperoxic animals inspired 100% O2 during the re-
suscitation phases. Neurobehavioral tests were conducted weekly
until the rats were perfused with fixative at 30 days post injury (dpi).
Brain sections were stained with Fluorojade B (FJB) and used for
stereology-based quantification to estimate contusion plus penum-
bral cortical volumes.
Survival was significantly greater following hyperoxic (84%)
compared to normoxic resuscitation (57%). Composite neuroscores
were higher with normoxic resuscitation at 21 dpi and balance beam
foot faults were significantly lower with normoxic resuscitation at 14
dpi. There was no difference in cortical pathology between the Nor-
moxic and Hyperoxic polytrauma groups.
The survival and general health of rats following CCI plus HS was
greater following hyperoxic resuscitation. In contrast, neurologic
outcomes were better following normoxic resuscitation.
Acknowledgments
This work was supported by USAMRMC Awards W81XWH-09-2-
0187 and W81XWH-07-2-0118.
Key words
hyperoxia, normoxia, polytrauma, shock
OC1-02
GLOBAL METABOLOMICS PROFILING REVEALS META-
BOLIC DYSREGULATION, OXIDATIVE STRESS AND NEU-
ROTRANSMISSION ALTERATION AFTER CONCUSSION
Deng-Bryant, Y., Leung, L.Y., Readnower, R., Yang, W., Shear, D.A.,
Tortella, F.C.
Walter Reed Army Institute of Research, Silver Spring, USA
Concussion is a mild form of trauma brain injury (TBI) that can lead
to long-term neurological deficits, and poses a risk factor for recurring
concussions. This study was designed to establish a temporal bio-
chemical profile following single or repetitive concussions, and to
identify biochemical processes that contribute to injury-associated
neuropathologies. Adult Sprague-Dawley rats were randomly as-
signed into three groups: sham (anesthesia), single projectile con-
cussive impact (sPCI), and repeated PCI (rPCI; 4 consecutive PCIs
spaced 1 hr apart). Ipsilateral frontal cortices were collected at 30min,
2 hr, 6 hr, 24 hr, 72 hr and 7 days post-sPCI, and at 2 hr post-rPCI
(n = 6/group/time-point). Mass spectrometry-based metabolomics
profiling revealed increased anaerobic glycolysis indicated by sig-
nificantly elevated glucose levels and glycogen metabolites in both
sPCI and rPCI tissues compared to sham controls. Significantly ele-
vated levels of glucose-6-phosphate and pentose phosphate pathway
(PPP) metabolites were only detected in the rPCI tissues, suggesting
an increase of glucose flux through PPP for tissue repair. Accom-
panied by higher levels of pyruvate and lactate, all PCI samples ex-
hibited significantly elevated levels of the tricarboxylic acid cycle
(TCA) intermediates citrate and alpha-ketoglutarate, but lower levels
of succinate compared to sham controls, suggesting impaired mito-
chondrial oxidation and free radical production. Relevant to this, both
sPCI and rPCI tissues exhibited significant reduction of carnosine and
glutathione levels, indicative of oxidative stress. Further, gamma-
aminobutyric (GABA) and acetylcholine levels trended higher in both
sPCI and rPCI tissues following injury. A significant increase of
glutamine was accompanied by lower levels of glutamate in both sPCI
and rPCI tissues, suggestive of excitotoxic injury. Overall, PCI sig-
nificantly altered the metabolic profile of the brain tissue, induced
oxidative stress and neurotransmitter changes. More importantly,
global metabolomics profiling was able to identify biochemical pro-
cesses that reflect an increased susceptibility to injuries following
rPCI, demonstrating that repetitive concussions exacerbate outcome
when occurring within a window of cerebral vulnerability.
Key words
concussion, glucose metabolism, metabolomics, oxidative stress
OC1-03
MITOCHONDRIA ASSOCIATED MICRORNA EXPRES-
SION IN HIPPOCAMPUS FOLLOWING TRAUMATIC
BRAIN INJURY
Wang, W.X.3, Visavadiya, N.P.1,2, Pandya, J.D.2,4, Nelson, P.T.3,5,
Sullivan, P.G.2,4, Springer, J.E.1,2,4
1University of Kentucky, Physical Medicine and Rehabilitation, Lex-
ington, KY
2Spinal Cord and Brain Injury Research Center, Lexington, KY
3Sanders-Brown Center on Aging, Lexington, KY
4Anatomy and Neurobiology, Lexington, KY
5Pathology, Lexington, KY
Traumatic brain injury (TBI) is a major cause of death and disability.
However, the molecular events contributing to the pathogenesis are
not well understood. Mitochondria serve as the powerhouse of cells,
respond to cellular demands and stressors, and play an essential role in
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