or 11.07 ng/mL (4XPCI). UCH-L1 peaked at 615.49 ng/mL (2XPCI).
Interestingly, there was strong correlation between GFAP and Tau
(
r
=
0.89) in 4XPCI cohorts. UCH-L1 correlated to Tau after 1XPCI
(
r
=
0.72) and 3XPCI (
r
=
0.98). Among all PCI cohorts, Tau and
UCH-L1, but not GFAP, correlated to RR (
r
=
0.41 and 0.30, re-
spectfully) as well as to composite NSS-R (
r
=
0.30 and 0.39, re-
spectfully). Both Tau and UCH-L1 aligned with tail reflex deficits
(
r
=
0.36–0.40), whereas Tau specifically correlated to ear-pinch
response deficits (
r
=
0.43) and increased UCH-L1 was in concert
with sound response deficits (
r
=
0.36). These results suggest that
single and repeated PCI are associated with specific CSF derived
biomarkers and neurological deficits, which may lead to critical
understanding the differential effects between single or repeated
concussions.
Keywords: Mild TBI, Concussion, CSF, GFAP, Tau, UCH-L1
A5-19
INVESTIGATION OF PUTATIVE ACUTE SERUM DIAG-
NOSTIC BIOMARKERS IN A PROJECTILE CONCUSSIVE
IMPACT INJURY
David Johnson
, Angela Boutte, Kara Schmid, Deborah Shear,
Jitendra Dave, Frank Tortella, Casandra Cartagena
Walter Reed Army Institute of Research, Psychiatry and Neu-
roscience, Silver Spring, USA
Investigation of microRNAs (miRNAs) as putative biological indi-
cators of injury has been examined in many disease states. MiRNAs
regulate many cellular processes through translational repression or
degradation. In this study we used the projectile concussive impact
(PCI) model and microarray platform to examine whether miRNAs
may serve as indicators of mild traumatic brain injury (mTBI). This
injury model represents a mild clinically relevant injury. Briefly, PCI
injury induction is a non-invasive, closed-head blunt impact to the
right temporoparietal region. Sham animals received equivalent an-
esthesia without impact. Serum was collected from rodents at 4h and
1d following injury and miRNA dysregulation was measured in ro-
dents. MicroRNA arrays were performed using Taqman megaplex
reverse transcription and pre-amplification kits. Each animal was run
as a single independent array (n
=
10/group). We limited our reporting
to miRNAs with p value
<
0.05 and a two-fold or greater change.
Given these criteria, we found one miRNA (miR-350) was signifi-
cantly decreased by 2.5 fold 4h post PCI. At 1d post PCI, four miRs
were upregulated including miR-Let 7f (2.1 fold), miR 190 (2.7 fold)
and miR 199a (7.4 fold). Interestingly, miR 350, which was initially
suppressed, was significantly increased nearly 3 fold at 1d post PCI.
These serum miRNA changes will be further studied to determine
their usefulness as both diagnostic and prognostic indicators of mTBI.
Additional studies will determine the temporal profile of miRNA
changes up to 7d post injury and whether specific miRNAs may serve
prognostic and/or theragnostics markers of mTBI at later time points
post-injury.
Keywords: microRNA, mild TBI, array
A5-20
DISCOVERING PROGNOSTICATORS FOR REPEATED
CONCUSSIONS: A GLOBAL METABOLOMIC STUDY
Ying Deng-Bryant
, Lai Yee Leung, Weihong Yang, Frank Tortella,
Deborah Shear
Walter Reed Army Institute of Research, Center for Military Psy-
chiatry and Neuroscience, Silver Spring, USA
Mild concussive injury can lead to a series of biochemical sequelae
that renders the brain vulnerable to a second concussion. Critically,
the time interval between the initial and the second concussion de-
termines the risk of exacerbated outcome. To test this hypothesis, this
study evaluated the effects of repeated concussions occurring at var-
iable intervals on biochemical alterations using global metabolomics.
Rats received two consecutive projectile concussive impacts (2
·
PCI)
at 6h, 24h, or 7d intervals; each paired with a procedure-matched
sham controls (anesthesia only). Cerebral cortices and cerebrospinal
fluid (CSF) were collected at 2h following the second PCI (n
=
7/
group). Metabolic profiling detected a total of 447 and 404 bio-
chemicals in brain tissue and CSF respectively. The percentage of
biochemicals that were significantly altered following 2
·
PCI
6
h,
2
·
PCI
24h
, and 2
·
PCI
7d
were 20.4%, 21.3%, 15.0% in the brain
(p
<
.05 vs. sham), and 23.3%, 7.4%, 5.0% in the CSF (p
<
.05 vs.
sham). These results suggest a differential threshold of the brain vs.
the CSF in response to concussion intervals with regards to the
number of biochemical alterations. Most notably, putrescine, a poly-
amine involved in endogenous tissue repair, showed the best prog-
nostic potential among all metabolites due to its high specificity to the
incidence interval of concussion. Cerebral putrescine levels, possibly
triggered by the injury for cellular regeneration, were significantly
increased (p
<
0.05) and negatively correlated with the concussion
intervals (i.e. shorter interval resulted in higher putrescine level;
R
2
=
0.6). As intracellular putrescine accumulated to potentially toxic
levels in brain tissue, its extracellular form, acetylputrescine, was
released into the CSF, leading to its elevation in both the brain and the
CSF and echoing the observed alterations of intracellular putrescine in
the same animals. Further, linear regression indicates that cerebral
acetylputrescine increased as the interval between concussions
shortened (R
2
=
0.6). Overall, these findings warrant further investi-
gation on the abundancy of putrescine associated metabolites in the
periphery circulation, hence the feasibility of developing a reliable
prognosticator(s) for concussion.
Keywords: Metabolomics, Concussion
A6 Poster Session II - Group A: Edema
A6-01
ACUTE HYDROCEPHALUS IN CERVICAL SPINAL CORD
INJURY: TWO DISTINCT PATHOPHYSIOLOGIC CAUSES
AND LITERATURE REVIEW
Tyler Atkins
1
, Sam Ford
2
, Joshua Patt
2
, Scott Wait
1
1
Carolinas Medical Center, Neurosurgery, Charlotte, USA
2
Carolinas Medical Center, Orthopaedic Surgery, Charlotte, USA
Cervical spinal cord injury (SCI) has well-known risks of clinical de-
cline from medical complications or less frequently, ascending spinal
deficits. Intracranial pathology, i.e., hydrocephalus, secondary to cer-
vical SCI however is extremely rare. We discuss two patients who
developed acute altered mental status and hydrocephalus following
cervical spine fracture with SCI. A literature review was performed
using PubMed: Medline to search for similar cases. Patient A, a 40 year-
old male, presented with Glasgow Coma Scale of 11T and C4 complete
SCI following a C4-5 fracture-dislocation. Twelve hours after urgent
posterior decompression and fusion, the patient became acutely coma-
tose. Head CT revealed moderate hydrocephalus and posterior fossa
edema. Ventriculostomy did not provide neurologic improvement. MRI
revealed acute ischemic stroke of the brainstem and cerebellum with
tonsillar herniation. Review of pre-operative MRI of the c-spine is
highly suggestive of bilateral vertebral artery occlusion due to absent
flow voids. Patient B, a 53 year old male, presented with an incomplete
A-36