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phagocytosis, TBI, and other regulatory mechanisms. In addition, a
dichotomized categorization when inputting the differentially ex-
pressed genes revealed over half of the patients could be correctly
clustered in their respective TMI
+
and TMI- groups. These findings
suggest that TMI may be a distinct, highly prevalent, phenotype that is
relevant to the pathogenesis of acute TBI.
Keywords: imaging, meningeal, biomarkers, gene-expression
C2-02
A COMPARATIVE STUDY ON SERUM MICRORNA BIO-
MARKER SIGNATURES OF MILD TRAUMATIC BRAIN IN-
JURY AND POSTTRAUMATIC STRESS DISORDER
Nagaraja Balakathiresan
1
, Raghavendar Chandran
1,4
, Manish
Bhomia
1
, Anuj Sharma
1
, Erin S. Barry
2
, Mary Anne Hutchison
2
,
Min Jia
3
, He Li
3
, Neil Grunberg
2
, Radha K. Maheshwari
1
1
Uniformed Services University of the Health, Pathology, Bethesda,
USA
2
Uniformed Services University of the Health, Department of Medical
and Clinical Psychology, Bethesda, USA
3
Uniformed Services University of the Health, Department of Psy-
chiatry, Bethesda, USA
4
Birla Institute of Technology and Science, (4) Biological Sciences
Group, Pilani, Rajasthan, India
Mild traumatic brain injury (mTBI) is often associated with post-
traumatic stress disorder (PTSD) in combat scenario as well as in
certain civilian cases. However, it is difficult to distinguish mTBI and
PTSD due to overlapping symptoms between them. The emerging
evidences of PTSD prevalence in combat soldiers suggest the im-
portance of developing sensitive and specific diagnostic markers for
PTSD and mTBI. MicroRNAs (miRNAs) are small, endogenous,
evolutionarily conserved noncoding RNA and the key regulators of
gene expression. Recently, circulating miRNAs in blood have been
reported to be sensitive and specific biomarkers of various diseases
and disorders including brain injury. In this study, we used a mouse
model of weight drop injury to recreate closed head TBI and a rat
learned helplessness stress model for PTSD. Serum was collected at
3 h following four different closed head injury (CH-TBI) groups and
3h and day 14 of PTSD. MiRNA profiling in serum showed thirteen
and nine common miRNAs among four CH-TBI groups and PTSD
serum and amygdala, respectively. However, the comparison of al-
tered serum miRNAs of CHI-TBI and PTSD showed no correlation.
Pathway analysis of thirteen miRNAs and their validated targets
showed few of them to have a direct correlation with axon guidance,
depression and sensorimotor impairment associated pathways. Com-
parison of altered serum miRNAs between CH-TBI and PTSD
showed no correlation. The difference in the serum miRNA expres-
sion signature could be an outcome of the different functional path-
ways activated post TBI or stress exposure in the brain which in turn
gets reflected in the alteration of the global serum miRNA profile.
These results suggest that miRNA signatures can be used for the
differential diagnosis of PTSD and TBI.
Acknowledgments
This work was supported by funding from DMRDP (PI: Radha K
Maheshwari). The opinions expressed herein are those of authors and
are not necessarily representative of those of the Uniformed Services
University of the Health Sciences (USUHS), the Department of De-
fense (DOD); or, the United States Army, Navy, or Air Force and
DMRDP
Keywords: miRNA, serum biomarker, TBI, PTSD, Differential
diagnosis
C2-03
TRANSCRIPTOMICS OF AGGRAVATED EPILEPTOGEN-
ESIS AND COGNITIVE DECLINE AFTER TBI IN APP/PS1
MOUSE MODEL OF ALZHEIMER’S DISEASE
Asla Pitkanen
1
, Diana Miszczuk
1,2
, Kondrad Debski
2
, Heikki Tanila
1
,
Katarzyna Lukasiuk
2
1
Univ. of Eastern Finland, Neurobiology, Kuopio Fin, Finland
2
Nencki Institute, Epilepsy Laboratory, Warsaw, Poland
Objectives:
To test the hypothesis that amyloidogenic genetic back-
ground predisposes to worsening of post-TBI outcome, we investi-
gated whether TBI in the APP/PS1 PS1 mouse model of AD
aggravates epileptogenesis, enhances somatomotor and cognitive
impairment, and associates with long-term changes in the expression
of genes involved in the amyloidogenic and Tau pathways.
Methods And Results:
Mild (mTBI) or severe TBI (sTBI) was
triggered using controlled cortical impact (CCI) in APP/PS1 mice and
wild-type (wt) littermates. Composite neuroscore showed that the TBI
severity but not APP/PS1 genotype had an effect on somatomotor per-
formance during the first 2 wk post-TBI (p
<
0.001). Morris water-maze
(MWM) revealed a genotype effect on TBI-induced impairment in
spatial learning and memory as APP/PS1-sTBI mice performed more
poorly than Wt-sTBI mice (p
<
0.05). Both TBI severity and genotype
affected epileptogenesis, as 88% of APP/PS1-sTBI mice had epilepsy
which was greater than that in the Wt-sTBI (11%, p
<
0.01) or APP/PS1-
sham group (50%, p
<
0.05). Gene expression profiling of the perilesional
cortex, ipsilateral thalamus, and ipsilateral hippocampus was performed
at 16 wk post-TBI using an Affymetrix microarray system. Of the 133
genes involved in the amyloidogenic and Tau pathways, sTBI induced
transcriptional changes in 17 genes in Wt mice and in 10 genes in APP/
PS1 mice. The seizure frequency correlated with the cortical expression
of Nos1 (r
=
0.83) and Mapk3 (r
=
0.67). Immunohistochemical analysis
confirmed increased expression of Nos1 protein in neuronal somata and
processes in the perilesional cortex of APP/PS1 mice as compared to
APP/PS1-sham (p
<
0.05) or Wt-sTBI groups (p
<
0.01). Motor impair-
ment correlated with the cortical expression of genes encoding amyloid
clearing proteins, such as Clu (r
=
0.83), Abca1 (r
=
0.78), A2m (r
=
0.76),
Apoe (r
=
0.70), and Ctsd (r
=
0.63).
Conclusions:
The present study provides the first comprehensive
evidence of the causal role of the AD genotype in the exacerbation
epileptogenesis after TBI.
Keywords: Alzheimer’s disease, epileptogenesis, post-traumatic
epilepsy, bioinformatics
C2-04
AEROMEDICAL EVACUATION-RELEVANT HYPOBARIA
WORSENS TBI IN RATS EXPOSED TO UNDERBODY
BLAST-INDUCED HYPERACCELERATION
Gary Fiskum
, Yi-Chun Hsieh, Julie Proctor, Alan Faden, Adam
Puche
Univ. of Maryland, Baltimore, Anesthesiology, Baltimore, USA
Occupants of vehicles targeted by IEDs are often victims of TBI and are
typically air-evacuated (AE) to a regional medical center within a few
days post-injury. This study tested the hypothesis that exposure of rats
to AE-relevant hypobaria worsens damage to white matter and blood
vessels caused by blast-induced acceleration. The underbody blast
paradigm (Proctor et al., 2012) resulted in peak vertical acceleration
of adult male rats equal to 100 Gs without exposure to blast over-
pressure. Rats remained under normobaric conditions or were exposed
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