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S10-02
CHRONIC NEUROPHYSIOLOGICAL RECORDING OF THE
HIPPOCAMPUS IN AWAKE BEHAVING SWINE AFTER
DIFFUSE BRAIN INJURY
Paul Koch
1
, Anand Tekriwal
1
, Alexandra Ulyanova
1
, Micheal
Grovola
2,1
, D. Kacy Cullen
2,1
,
John Wolf
2,1
1
University of Pennsylvania, Dept. of Neurosurgery, Philadelphia,
USA
2
Philadelphia VA Medical Center, Dept. of Neurosurgery, Philadel-
phia, USA
We have previously established an acute recording methodology to in-
terrogate hippocampal circuitry after diffuse brain injury (DBI) in a
swine model of rotational injury. Injuries were administered over a range
of coronal rotational accelerations (180260 rad/sec) that induced little or
no loss of consciousness (
<
15min), yet exhibited axonal pathology.
Limitations of electrophysiological recording under anesthesia have led
us to develop a chronic hippocampal electrode implantation model in the
awake, freely moving swine, allowing examination of hippocampal
networks engaged in relevant behavior after injury. Repeated concurrent
electrophysiological and behavioral measures enable examination of
how network level interactions may be disrupted after DBI. We have
developed a stereotaxic surgical technique for precise implantation of a
custom 32-channel silicone electrode into the swine hippocampus that
allows for recordings of both single units in layer CA1 and dentate, as
well as simultaneous laminar field potentials while the animal is awake
and freely moving during behavioral tasks. We have also developed a
novel object recognition task for swine, a behavior known to be hippo-
campal dependent. Pigs were trained on this task prior to electrode im-
plantation. Preliminary behavioral results indicate that sham injured
swine reliably interact longer with novel objects versus familiar objects.
Moreover, we demonstrate robust extracellular field potentials out to 5
months post-implantation, as well as stable unit recordings pre- and post-
implantation. Using spectral density analysis we report a prominent peak
in hippocampal theta rhythm power in the freely behaving pig with
positive shifts in peak frequency and peak power during periods of lo-
comotion. This dominant hippocampal rhythm has previously been
shown to be disrupted in rodent traumatic brain injury models. Here we
demonstrate the feasibility of combining chronic hippocampal electro-
physiological recordings with concurrent behavior in freely moving large
animals. Combining this methodology with our established DBI model in
pigs may reveal mechanisms of trauma-induced network dysfunction
which may lead to innovative neuromodulatory therapies.
Keywords: electrophysiology, behavior, rotational injury, mild TBI
S10-03
ABBREVIATED ENVIRONMENTAL ENRICHMENT CON-
FERS ROBUST NEUROBEHAVIORAL AND COGNITIVE
BENEFITS IN BRAIN INJURED FEMALE RATS
Hannah Radabaugh
1
, Jeffrey Niles
1
, Lauren Carlson
1
, Christina
Monaco
1
, Jeffrey P. Cheng
1
, Naima Lajud Avila
1,2
, Corina O. Bondi
1
,
Anthony E. Kline
1
1
University of Pittsburgh, Physical Medicine & Rehabilitation and
Safar Center for Resuscitation Research, Pittsburgh, USA
2
Instituto Mexicano del Seguro Social, Laboratorio de Neurobiologı´a
del Desarrollo, Morelia, MX
To establish an efficacious therapy for traumatic brain injury (TBI) a
variety of relatively invasive strategies have been evaluated. Environ-
mental enrichment (EE) is a non-invasive paradigm that promotes sig-
nificant cognitive recovery after experimental TBI and has the potential to
mimic post-TBI neurorehabilitation. However, the typical EE paradigm
consists of continuous exposure, which is inconsistent with the clinic
where physiotherapy is typically limited (Matter et al., 2011). Moreover,
females make up approximately 40% of the clinical TBI population, yet
they are rarely studied in TBI research. Hence, the goal of this study was
to
test the hypothesis that abbreviated EE would confer neurobehavioral
and cognitive benefits in brain injured female rats
. Anesthetized female
rats received a controlled cortical impact (2.8mm tissue deformation at
4m/s) or sham injury (i.e., no impact) and were randomly assigned to
TBI
+
EE (4 hr), TBI
+
EE (6 hr), TBI
+
EE (continuous), or TBI
+
STD
groups, and respective sham controls. Motor function (beam-balance/
beam-walk and rotarod) was assessed on post-operative days 1–5 and
every other day from 1–19, respectively. Spatial learning/memory
(Morris water maze) was evaluated on days 14–19. The data showed that
EE, regardless of dose, improved motor function compared to STD
housing (
p
<
0.0001). However, only continuous and 6-hr EE enhanced
cognitive function (
p
<
0.0001). These data demonstrate that abbreviated
EE confers robust neurobehavioral and cognitive benefits in TBI female
rats, which supports the hypothesis and strengthens the validity of EE as a
pre-clinical model of neurorehabilitation. Ongoing studies from our
laboratory are evaluating further the benefits of abbreviated EE by
combining it with pharmacotherapies, which may result in additive or
synergistic benefits, thus facilitating recovery after TBI.
Keywords: Brain Injury, Controlled Cortical Impact (CCI), En-
vironmental Enrichment, Females
S10-04
NEUROINFLAMMATORY MYELOID CELL PROCESSES
ASSOCIATE WITH DIFFUSELY INJURED AXONS FOL-
LOWING MILD TRAUMATIC BRAIN INJURY IN MICRO-
PIGS
Audrey Lafrenaye
, Masaki Todani, John Povlishock
Virginia Commonwealth University, Anatomy and Neurobiology,
Richmond, USA
Mild traumatic brain injury (MTBI) is a prevalent disease that exacts
significant personal and societal cost. The pathophysiology of MTBI is
complex, with reports of diffuse axonal injury (DAI) being highly cor-
related to prolonged morbidity. Progressive chronic neuroinflammation
has also recently been correlated to morbidity, however, the potential
association between neuroinflammatory myeloid cells and DAI is not well
understood. The majority of studies exploring neuroinflammatory re-
sponses to TBI have focused on more chronic phases of injury and
phagocytosis associated with Wallerian change. Little, however, is known
regarding the neuroinflammatory responses seen acutely following diffuse
MTBI and potential relationships to early DAI, an issue that has signifi-
cant clinical relevance. Additionally, inflammation has recently been
shown to be drastically different in rodents as compared to gyrencephalic
humans. Accordingly, we employed a modified central fluid percussion
model of MTBI in gyrencephalic micropigs and assessed potential asso-
ciations between acute DAI and neuroinflammation within 6h of injury.
This model generated substantial DAI in the thalamus (10.31
–
1.34 APP
+
swellings/0.72mm
2
field), an area commonly affected across the spectrum
of TBI. Extensive neuroinflammation was also observed following MTBI
in the same thalamic sectors. Importantly, physical contact between Iba-
1
+
myeloid cell processes and the APP
+
swellings of axons sustaining
DAI was nearly double (0.16
–
0.02 contacts/mm) compared to uninjured
myelinated axons in sham animals (0.09
–
0.01 contacts/mm). While ac-
tive phagocytosis was observed in association with Wallerian degenera-
tion, the Iba-1
+
cells that contacted DAI swellings did not reveal
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