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targeted 1-MHz pulsed high intensity focused ultrasound (pHIFU)
system was applied to adult ZF to create the first closed-head injury
model in ZF.
Results:
Automated behavioural testing and Western blot analysis
of susceptible white matter proteins expression demonstrated dose-
dependent response to ultrasound injury. The model also demon-
strated responsiveness to two interventions (hypothermia and hypoxic
preconditioning) shown to be effective in other models of TBI.
Conclusions:
Our results indicate that the ZF response to brain
trauma exhibits similar mechanisms of secondary injury to mammalian
pathophysiology. Our model can be used to rapidly screen potential
therapeutic candidates. This is an important novel tool for investigating
the mechanisms of downstream neuronal death, and for the rapid im-
plementation of large-scale preclinical drug evaluation for TBI.
Keywords: Zebrafish
D2-13
IMMUNE CELL ACTIVATION UNDERLYING LEARNING
AND MEMORY IMPAIRMENT IN THE JUVENILE FEMALE
RAT AFTER REPEAT CLOSED HEAD INJURY
Alicia Meconi
, Brian Christie
University of Victoria, Division of Medical Sciences, Victoria, Ca-
nada
It is well understood that sustaining multiple mild traumatic brain injuries
(mTBI) can increase risk for suffering more persistent and severe
symptoms, yet the physiological cause of this increased risk remains
unclear. Recent work on this problem has focused primarily on adult
male subjects, despite clinical evidence suggesting that that mTBI out-
comes may be worse in females and in children. To investigate this
critical issue in these populations of interest, we developed a clinically-
relevant closed head injury model to induce repeat mild traumatic brain
injury in rodents. This model was used to induce single and repeat mTBI
in juvenile female rats in order to characterize the pathophysiological
processes underlying learning and memory impairment, a common
mTBI symptom. Postnatal day 25–28 female rats received a single closed
head mTBI, or four mTBIs over 26 hours, and a control group received
sham mTBIs. Spatial learning and memory were assessed in the Morris
water maze on the second to seventh day after the final impact. At seven
days post-impact these rats were sacrificed and their brains were ex-
tracted for histological assessment. FluoroJade-C staining and caspase3
immunohistochemistry were used to detect necrotic and apoptotic cell
death in the hippocampus. Immunohistochemical staining of GFAP and
Iba1 were used detect activation and recruitment of astrocytes and mi-
croglia, respectively, in the hippocampus. Preliminary findings show that
repeat mTBI leads to impaired learning and memory in the Morris water
maze, accompanied by immune cell activation and cell death in the
hippocampus. These findings show that this closed head injury model is
able to reliably produce mTBI symptoms and pathology that reflect those
seen in clinical populations. Future investigations will characterise a time
course of these processes in the first week after single and repeat mTBI.
Keywords: repeat mTBI, closed head injury, learning and memory,
pediatric mTBI
D2-14
MECHANICAL RESPONSE OF SWINE EXPOSED TO FREE-
FIELD BLASTS
Liying Zhang
, Ke Feng, Chaoyang Chen, Xin Jin, Srinivas Kallakuri,
John Cavanaugh, Albert King
Wayne State Univ, Biomedical Engineering, Detroit, USA
The mechanism of blast induced traumatic brain injury (BTBI) is not
well understood. BTBI caused by explosion represents the response of
brain to the initial blast waveform. Experimental data on live animals
provides indispensable information of brain neurotrauma caused by
blast exposure. However, there is little knowledge on the biome-
chanical responses of the brain subjected to primary free-field blast
waves in large
in vivo
animal models. This study presents a swine
model of primary blast injury to the brain. The incident blast over-
pressure (IOP) was generated using 8 lbs of C4 charges detonated at
various stand-off distances to the forward facing anesthetized male
Yucatan swine (50–60 kg, ages 6–8 months). The average peak IOP in
the three free-field blast groups were 148.8 kPa (low), 278.9 kPa
(medium), and 409.2 kPa (high). The mechanical responses of the
brain were recorded with intracranial pressure (ICP) sensors placed on
the surface of the brain at 4 locations (frontal, parietal, left and right
temporal, occipital lobe) and the center of the brain. The head kine-
matics were recorded with tri-axial linear accelerometers and tri-axial
angular rate sensors installed on a block with rigid attachment to the
skull. ICP peak values (94–140 kPa, 210–282 kPa, and 312–420 kPa)
at the various brain locations were increased with IOP levels. None-
theless, there was no significant difference in peak values at different
locations of the brain at the same IOP level. Peak resultant head
acceleration (175–636 g) correlated well with peak IOP. The durations
of the linear acceleration and angular velocity were typically less than
3 ms with very little head motion. The results of this model provide
initial detailed response data of swine brain during exposure to pri-
mary blast waves. The experimental data can be used to validate
computer models. When combined with injury data in parallel studies
the ICP responses at different blast levels can be used to help deter-
mine injury mechanisms and thresholds of the brain subjected to
primary blast.
Keywords: Primary blast induced brain injury, Swine model, Open-
field blast, Intracranial pressure measurement, Head acceleration and
velocity,
D3 Poster Session VII - Group D:
Neurotransplantation
D3-01
SURVIVAL AND BIODISTRIBUTION OF HUMAN FETAL
NEURAL STEM CELL TRANSPLANTS IN PENETRATING
BALLISTIC BRAIN INJURY (PBBI)
Shyam Gajavelli
1
, Markus Spurlock
1
, Aminul Ahmed
1
, Karla
Rivera
1
, Lai Yee Leung
3
, Deborah Shear
3
, Shoji Yokobori
2
, Frank
Tortella
3
, Tom Hazel
4
, Ross Bullock
1
1
University of Miami, Miami Project to Cure Paralysis, Miami, USA
2
Department of Emergency and Critical Care Medicine, Nippon
Medical School, Tokyo, Japan
3
Brain Trauma Neuroprotection and Neurorestoration, Center for
Military Psychiatry and Neuroscience, Walter Reed Army Institute of
Research, Silver Spring, USA
4
Neuralstem Inc, Neuralstem Inc, Germantown, USA
Introduction:
Penetrating traumatic brain injuries (PTBI) are asso-
ciated with the worst outcomes with both high mortality and severe
disability. While no treatment strategies are available, neural stem cell
transplantations have emerged as putative therapeutic approach. In
this rodent study, we evaluated the biodistribution of FDA approved
human fetal neural stem cells (hNSC; Neuralstem Inc.) in a rat model
of PTBI: Penetrating ballistic brain injury (PBBI).
Methods:
Adult Sprague-Dawley rats underwent a unilateral pen-
etrating ballistic brain injury (PBBI). Immunosuppression was es-
A-105