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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