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A2-09
THE INCIDENCE RATE OF MILD TRAUMATIC BRAIN IN-
JURY IN PATIENTS SUFFERING FROM AN UPPER OR
LOWER LIMB FRACTURE
Marianne Jodoin
1,2
, Louis De Beaumont
2,3
, Jean-Franc¸ois Gigue`re
2
,
Nadia Gosselin
1,2
, Dominique Rouleau
2
1
Universite´ de Montre´al, De´partement de Psychologie, Montre´al,
Canada
2
Hoˆpital du Sacre´-Coeur, Centre de Recherche, Montre´al, Canada
3
Universite´ de Trois-Rivie`re, De´partement de Psychologie, Trois-
Rivie`re, Canada
Orthopaedic traumas (e.g., limb fractures) typically caused by accidental
falls or traffic road accidents generally require immediate surgical in-
tervention. Loss of articular amplitude and motor weakness persist in
some patients with no apparent anatomical abnormalities. Interestingly,
mild traumatic brain injury (mTBI) present similar sequelae suggesting a
connection between the two. Hence, it is possible that the severity of the
fracture silence the otherwise apparent symptoms of mTBI, therefore
preventing early detection. This study compares the incidence of con-
comitant mTBI detected at follow-up visits in a Level I Trauma Hospi-
tal’s orthopaedic clinic with the incidence held by the hospital records.
This study also seeks to determine which types of fractures and accidents
present the highest incidence of mTBI.
Methods:
150 orthopaedic monotrauma patients were retrospectively
assessed for mTBI through standardized semi-structured interviews.
Results:
The incidence rate of mTBI accompanying upper limb
fractures was 28% and 24% for lower limb fractures compared to the
hospital incidence rates of 22% and 9%, respectively. Collarbone
fractures presented the highest incidence rate with 64%. Among all
types of accidents, high velocity accidents (e.g., traffic road accidents)
presented the highest incidence rate with 79% compared to low velocity
accidents (e.g., accidental falls) that showed an incidence rate of 11%.
Conclusion:
Although preliminary, results suggest that a high rate
of mTBI is undiagnosed in orthopaedic trauma patients, especially
with lower limb fractures. Finally, the results reveal the importance of
accounting for both the type of fracture and the type of accident, as
incidence rates vary greatly.
Keywords: Mild traumatic brain injury, Orthopaedic Trauma, In-
cidence rate
A2-10
CALCIUM AND GLUTAMATE SIGNALING AFTER TBI
VISUALIZED IN-VITRO USING GENE-ENCODED MOLE-
CULAR SENSORS GCAMP6 AND IGLUSNFR
Robert Berman
1
, Shiwei Huang
3
, Jazmine Liew
3
, Bruce Lyeth
1
, Lin
Tian
2
,
Gene Gurkoff
1
1
University of California, Davis, Neurological Surgery, Davis, USA
2
University of California, Davis, Biochemistry and Molecular Medi-
cine Psychiatry and Behavioral Sciences, Davis, USA
3
Drexel University, Masters of Medical Science Program, Sacra-
mento, USA
An estimated 3.6 million Americans experience traumatic brain injury
(TBI) annually, and effective treatments to improve neurological out-
come following TBI are not yet available. Development of successful
interventions requires a better understanding of the cellular mechanisms
that lead to cell death and impaired neural function. Altered calcium and
glutamate signaling are among the many sequelae associated with TBI,
contributing to secondary cell injury and death. In addition, voltage gated
calcium channels (VGCCs), including N-type VGCCs, play a critical
role in the rise in intracellular calcium and the activation of calcium-
dependent pathways leading to neuronal injury and death. However,
previous data related to changes in calcium levels after TBI have come
from acute studies using 45Ca autoradiography, ion-selective micro-
electrodes and calcium-sensitive dyes (e.g., Fura-2). Such techniques do
not provide longitudinal information on changes in calcium levels that
occur over the hours to days following TBI. Therefore, we initiated a
series of studies using gene encoded molecular sensors (GEMS) that
allow for long-term and repeated calcium and glutamate imaging
in vitro
and
in vivo
. We used the GEMS GCamP6 to visualize intracellular
neuronal calcium-signaling in an
in vitro
model of TBI, imaging the same
cells over 48 hours. Following injury there was a rapid rise in intracellular
calcium that returned to near baseline levels over 48 hours. SNX-185, a
synthetic
x
-conopeptide and VGCC blocker, reduced the frequency and
amplitude of calcium spikes prior to injury, and reduced calcium accu-
mulation post-injury. Longitudinal imaging of calcium and glutamate in
the same cells over extended periods of time using GEMS will allow
better characterization of the pathophysiology of TBI. The technology
also provides a high-throughput screening platform for compounds that
may have therapeutic potential in the treatment of TBI.
Keywords: Gene Encoded Sensors, Longitudinal, Voltage Gated
Calcium Channel Blockers
A2-11
A ‘‘NEET’’ MITOCHONDRIAL TARGET FOR TBI: THE IM-
PORTANCE OF MITONEET IN PIOGLITAZONE MEDIATED
NEUROPROTECTION
Heather Yontuas
1,2
, Jignesh Pandya
2
, Andrea Sebastian
2
, Werner
Geldenhuys
3
, Richard Carroll
3
, Patrick Sullivan
1,2
1
University Of Kentucky, Anatomy and Neurobiology, Lexington, USA
2
University Of Kentucky, Spinal Cord and Brain Injury Research
Center, Lexington, USA
3
Northeast Ohio Medical University, College of Pharmacy, Roots-
town, USA
Traumatic Brain Injury (TBI) is difficult to treat due to the compli-
cated secondary injury cascade that ensues following the initial insult.
The most promising therapeutics are multi-targeted, improving neu-
roinflammation, ROS production and mitochondrial dysfunction.
Pioglitazone, an FDA approved drug for Type 2 Diabetes and known
PPAR agonist, has shown promise in altering neuroinflammation and
decreasing ROS production. Work from our lab found that pioglita-
zone can increase mitochondrial bioenergetics within the first 12 to 24
hours post-injury. This effect, too rapid to be mediated through PPAR
alone, may be dependent on its ability to bind a novel mitochondrial
protein called mitoNEET. Therefore, we hypothesize that pioglitazone
is a mitoNEET specific ligand that binds mitoNEET to improve mi-
tochondrial bioenergetics leading to increased cortical sparing and
functional recovery. To test this hypothesis we used a severe Con-
trolled Cortical Impact (CCI) injury model, mitoNEET null and wild-
type mice, pioglitazone and a novel mitoNEET ligand called NL-1,
which is a truncated analogue of pioglitazone with no PPAR binding
region. When simulating Ca
2
+
induced excitotoxicity, pioglitazone
can increase bioenergetics in naı¨ve isolated cortical mitochondria
following insult with Ca
2
+
(n
=
3; p
<
0.05). An
in-vivo
pioglitazone
(n
=
9) and NL-1 (n
=
4) dose-response study was then preformed in
wild-type mice post-injury. The dosages with the greatest ameliora-
tion of mitochondrial dysfunction were used in wild-type and mito-
NEET null mice following a sham or severe CCI surgery. At these
dosages, pioglitazone lost its ability to increase mitochondrial respi-
ration (n
=
3) and provide neuroprotection (n
=
6) in mitoNEET null
mice. Additionally, NL-1 decreased MRI T2-weighted hyperintensity
at the injury site and increased cortical sparing (n
=
6, p
=
0.03) and
A-22