CBF reductions with normal MAP suggest BINT significantly in-
creased cerebral vascular resistance. Additionally, impaired vasodila-
tion in MCA segments suggests autoregulation impairment by BINT.
These observations suggest BINT is associated with significant cerebral
vascular injury. BINT-induced increases in EB extravasation indicate
an acute breakdown of BBB that was reversed by ONOO
-
scavenging,
suggesting a role of ONOO- in BINT-induced BBB dysfunction.
Key words
behavior, blast injury, blood-brain barrier permeability, peroxynitrite
D2-06
A NEW RODENT MODEL OF PEDIATRIC SPORTS-RELATED
CONCUSSION
Avitua, A.
, Shafique, H., Echeverri, A.M., Seidl, S.E., Yin, H.,
Zwienenberg-Lee, M., Gurkoff, G.G.
University of California, Davis, Department of Neurological Surgery,
Davis, USA
CDC data indicates that over 50% of all traumatic brain injury (TBI)
occurs in individuals less than 24 years old. The majority of these in-
juries are mild and, increasingly, they are sports-related. In order to
model a sports-related injury we attached a metal disc directly to the
skull and then impacted this disc using the controlled cortical impact
device. The metal disc acts as a helmet to diffuse the force across the
skull allowing for concussive injury in the absence of skull fracture. To
test this model in the p35 rat, we generated a range of injuries by using a
fixed depth of penetration (5mm) and varying the piston velocity from 2
to 5m/s. To assess outcome, we compared performance on the rotarod,
ladderwalk, and Morris water maze between injured rats and sham
controls in the first 10 days following injury. Regardless of piston ve-
locity, animals experienced minimal periods of unconsciousness, and
were ambulatory within 15 minutes. Animals with a 2m/s injury (mild)
had neither a motor nor spatial learning deficit. Animals with a 5m/s
injury (moderate) also displayed no motor deficit; however, latency to
find the hidden platform in the water maze was significantly increased
(p
<
0.05) as compared to sham animals. Based on these initial data we
included two additional groups with repeat injury: mild
+
mild or
mild
+
moderate with a 1 hour inter-injury interval. Similar to the single
injuries, no significant motor deficits were observed. Surprisingly, both
groups performed similar to sham animals in the water maze. It is clear
from both clinical experience and these current data that impacts onto a
helmet can create a concussive injury leading to cognitive deficits. Our
data also highlights the complexity and diversity of outcome observed
following repeat concussive injury. Therefore, further development of
animal models is critical to our understanding of how to care for young
patients who have experienced concussions due to a sports-related injury.
Key words
repeat concussion, sports-related injury
D2-07
ELUCIDATING THE KINEMATICS AND PATHOBIOLOGY
OF BLAST-RELATED TRAUMATIC BRAIN INJURY AND
SEQUELAE IN A MOUSE MODEL
Wojnarowicz, M.W.
1
, Fisher, A.M.
1
, Tagge, C.A.
1
, Gaudreau, A.B.
1
,
Minaeva, O.
1
, Moncaster, J.A.
1
, Casey, N.
1
, Stein, T.D.
1–3
, Moss,
W.C.
4
, Moir, R.D.
6
, Tanzi, R.E.
6
, Stanton, P.K.
5
, McKee, A.C.
1–3
,
Goldstein, L.E.
1,2
1
Boston University School of Medicine, College of Engineering,
Boston, USA
2
Boston University Alzheimer’s Disease Center, Boston, USA
3
Boston VA Healthcare System, Boston, USA
4
Lawrence Livermore National Laboratory, Livermore, USA
5
New York Medical College, Valhalla, USA
6
Massachusetts General Hospital, Charlestown, USA
Traumatic brain injury (TBI) resulting from blast exposure is a leading
cause of death and disability associated with the recent military con-
flicts in Iraq and Afghanistan. We and others have reported evidence
that links sports-related TBI with later development of chronic trau-
matic encephalopathy (CTE), a tau protein-linked neurodegenerative
disease (Omalu, 2005, 2006, 2010; McKee, 2009, 2010, 2013). We
previously reported the first case series of postmortem brains from
blast-exposed military veterans and found evidence of CTE neuropa-
thology that was indistinguishable from the neuropathology observed in
brains from the youngest athletes with verified CTE studied to date
(Goldstein, 2012). In the same study, we showed that C57BL/6 mice
exposed to a single blast developed CTE-linked neuropathology, ax-
onopathy, microvasculopathy, and neurodegeneration (Goldstein,
2012). Blast-exposed mice demonstrated persistent cognitive deficits
that correlated with impaired axonal conduction and defective synaptic
neurotransmission in the hippocampus. Collectively, these abnormali-
ties recapitulate core clinical features of TBI and CTE in humans
(Stern, 2013). Here we used metallomic imaging mass spectrometry,
flow cytometry, cortical slice electrophysiology, and neurobehavioral
testing to show that single blast exposure induces blood-brain barrier
dysfunction, peripheral monocyte infiltration, chronic neuroinflamma-
tion, and defective cortical neurotransmission in blast-exposed mice.
Two-axis high-speed videography (10
l
sec capture rate; 100 kHz)
conducted during blast exposure or a kinematically-equivalent me-
chanical analogue confirm the pathogenic contribution of traumatic
head acceleration to acute and chronic effects of blast neurotrauma.
These results provide additional mechanistic evidence linking blast
exposure to acute TBI and chronic sequelae, including CTE.
Key words
blast, CTE, murine model, neuropathology
D2-08
BLAST-INDUCED TBI IN MICE ELICITS A BIPHASIC DE-
CREMENT IN THE PERG THAT CORRELATES WITH
RETINAL GANGLION CELL ACTIVITY
Harper, M.M.
1,2
, Yin, T.
2
, Pieper, A.
1,2
, Dutca, L.M.
2
, Blodi, F.R.
2
,
Shankar, M.
2
, Kardon, R.H.
1,2
, Stasheff, S.
2
1
Veterans Affairs, Iowa City, USA
2
University of Iowa, Iowa City, USA
Our goal was to determine whether retinal ganglion cells (RGCs) are
damaged by blast-mediated traumatic brain injury (TBI)
After blast-mediated TBI, analysis of RGC structure and function
was performed using optical coherence tomography (OCT) and pat-
tern electroretinogram (PERG) 7 days, 5 weeks and 4 months later.
Individual RGC physiology was monitored using a multielectrode
array (MEA). Spontaneous and light-evoked responses for each RGC
were measured at each time point. Dendritic arborization of individual
RGCs was analyzed using GFP-labelled RGCs.
PERG amplitude decreased 7 d after blast injury, which recovered
to baseline 5 weeks post injury. PERG was significantly decreased 4
months post injury. Decreased thickness of the RGC complex layer
was observed by OCT at each time point.
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