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A4-04
LARGE-ANIMAL COMBINED INSULT MODEL FOR IN-
FLICTED BRAIN INJURY IN INFANCY
Beth Costine
, Colin Smith, Monica Shifman, Declan McGuone,
Carter Dodge, Ann-Christine Duhaime
Massachusetts General Hospital/ Harvard Medical School, Neuro-
surgery, Boston, USA
Research elucidating the pathophysiology of non-accidental trauma in
infants and young children has been limited by the lack of appropriate
translational models. While widespread, diffuse bilateral brain damage
can be created readily by a number of global insults, infants with subdural
hematoma may have extensive unilateral damage (‘‘hemispheric hypo-
density’’) with sparing of the opposite hemisphere. Here we describe
tissue damage in our model of abusive head trauma. Piglets age 7–30 days
(n
=
18) were anesthetized and underwent cortical impact, mass effect via
epidural balloon inflation, unilateral subdural hemorrhage, and multiple
rounds of apnea, hypoventilation, and seizures induced with intravenous
bicuculline or a sham surgery was performed (n
=
5). After injury, piglets
survived under anesthesia for up to 24 hours, with some subjects under-
going CT or 3T MRI. Brains were examined for neuronal death. Injection
of subdural blood after mechanical brain deformation enabled placement
of a large but thin unilateral hematoma, similar to those seen in human
children, in 90% of subjects, likely due to traumatic separation of the dural
border cells. Seizures lasted 20.25
–
6.2 minutes and were accompanied by
tachycardia, elevated mean arterial pressure, and decreased oxygen satu-
ration. During apnea and hypoventilation, subjects developed transient
hypotension, bradycardia, and hypoxia, followed by persistent alterations
in mean arterial pressure and reduced arterial pH. Asymmetric edema in
the affected hemisphere was demonstrated in a subset of subjects via
imaging and/or necropsy. To date, the density of damaged neurons in the
CA4 region of the hippocampus may be greater ipsilateral vs. contralateral
to the subdural hematoma. This is the first immature large-animal model
using the combined physiologic insults experienced by children with se-
vere inflicted traumatic brain injury with unilateral subdural hematoma
and asymmetric brain damage. Further studies with this model will fa-
cilitate exploration of the pathophysiology and possible treatments for this
common and highly morbid injury pattern unique to infants and toddlers.
Keywords: Abusive Head Trauma, Seizures, Brain Pathology, Swine
A4-05
MAGNETIC RESONANCE SPECTROSCOPY IMAGING OF
THE HIPPOCAMPUS AT 7T AFTER MILD TBI IN IMMATURE
BRAIN
Hulya Bayir
1
, Emin Fidan
1
, Lesley Foley
2
, Lee Ann New
1
, Patrick
Kochanek
1
, T. Kevin Hitchens
2
1
Safar Center for Resuscitation Research, Critical Care Medicine,
Pittsburgh, USA
2
Carnegie Mellon University, Pittsburgh NMR Center for Biomedical
Research, Pittsburgh, USA
Mild traumatic brain injury (mTBI) in children is a common and serious
public health problem. Traditional structural neuroimaging techniques are
often normal in children who sustain mTBI putting them at risk for re-
peated episodes of mTBI (rmTBI). There is a need for non-invasive and
more sophisticated imaging techniques capable of detecting changes in
neurophysiology after injury. In this study we examined metabolite
changes in immature brain resulting from mTBI and rmTBI using proton
magnetic resonance spectroscopy (
1
H-MRS). Eighteen day old male rats
were divided into three groups; Sham (n
=
8), mTBI (n
=
9, single impact),
rmTBI (n
=
10-three impacts 24h apart). The hippocampus in each rat was
examined at 7 Tesla, 7 days post injury. After mTBI and rmTBI, N-
acetylaspartate/creatine ratio (NAA/Cr) was significantly reduced
(p
=
0.03, p
<
0.0001, respectively), and the myo-inositol/creatine ratio
(Ins/Cr) significantly increased (p
=
0.017, p
=
001, respectively) compared
to sham controls. The choline/creatine (Cho/Cr) and lipid/creatine (Lip/Cr)
ratios were significantly decreased (p
=
0.04, p
=
0.02, respectively) after
rmTBI vs. sham. There was a small, but significant, further reduction
(p
=
0.01) in the NAA/Cr after rmTBI vs. mTBI. NAA/Cho was not sig-
nificantly different between injured vs. sham rats. We conclude that there is
alteration in NAA and Ins after mTBI and rmTBI likely reflecting neu-
roaxonal cell damage and glial proliferation, respectively. The decrease in
Cho and Lip after rmTBI may reflect damage to axonal membrane and
parallels the axonal argyrophilia observed in hippocampal region with
silver staining at d7 after injury. These findings may be relevant to un-
derstanding the extent of disability following mTBI in the immature brain.
Support: NS061817, NS076511.
Keywords: MRS
A4-06
CHRONIC WHITE MATTER DAMAGE FOLLOWING PE-
DIATRIC TRAUMATIC BRAIN INJURY
Jesse Fischer
1,2
, Dana DeMaster
2
, Juranek Jenifer
2
, Cox Charles
2
,
Kramer Larry
2
, Hannay H. Julia
1
, Ewing-Cobbs Linda
2
1
UH, Psychology, Houston, USA
2
UTHMC, Pediatrics, Houston, USA
Objective:
Differences in white matter integrity in children and ad-
olescents with traumatic brain injury (TBI) in the post-acute and
chronic stage was investigated; hypothesizing that children with TBI
would demonstrate significantly lower fractional anisotropy (FA),
compared to extracranial injury (EI) and typically developing (TD)
groups in the corpus callosum and frontal and temporal lobes.
Methods:
Diffusion tensor imaging was utilized to examine be-
tween-group differences in white matter integrity 6-weeks and 12-
months post-injury in children and adolescents aged 8–15 with TBI
(
n
=
10; 3 mild, 2 moderate, 5 severe;
M
=
12.4 yr; SD
=
2.2), EI
(
n
=
10;
M
=
12.7 yr; SD
=
2.8), and a TD group (
n
=
11;
M
=
12.0 yr;
SD
=
2.4). Groups did not differ significantly by IQ or age.
Data were acquired on a Philips 3T MR scanner. Scans were
manually checked for motion. The standard FSL pipeline was used for
Tract-Based Spatial Statistics analysis. Statistical comparisons using
the FSL RANDOMISE function were used to generate two-sample
T-tests comparing FA between groups controlling for age.
Results:
6-weeks post-injury, results demonstrated lower FA in the
TBI group than the TD group throughout frontal, temporal, and pa-
rietal regions, primarily in the corpus callosum, longitudinal fasciculi,
cerebellum and cingulum (
p
<
.05). Additionally, FA remained sig-
nificantly lower in the TBI group at 12-months, specifically in the
anterior corona radiata, cingulum, superior longitudinal fasciculus,
and corpus callosum (
p
<
.05).
When comparing TBI and EI groups, FA was significantly lower in
the TBI group at 6-weeks, specifically in the fronto-occipital fasciculi,
genu of the corpus callosum, left superior longitudinal fasciculus, and
cingulum (
p
<
.05). However, there were no significant differences
between TBI and EI groups at 12-months. No differences in FA were
evident between TD and EI groups.
Conclusion:
Following pediatric TBI, white matter integrity dam-
age is evident at 6-weeks and remains 1-year post-injury. Findings
indicate long-lasting effects of TBI in the cingulum, superior longi-
tudinal fasciculi, and corpus callosum with some recovery between
the acute and chronic stages.
Keywords: Diffusion Tensor Imaging, WhiteMatter Integrity, Pediatrics
A-28