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Open Communications
S10 Open Communication: TBI
S10-01
PREVENTING POSTTRAUMATIC EPILEPTOGENESIS BY
STIMULATING CORTICAL EXCITATORY ACTIVITY
AFTER TRAUMATIC BRAIN INJURY
Xiaoming Jin
1,2
, Xingjie Ping
1,2
, Wenhui Xiong
1,2
, Grace Chavez
1,2
,
Jianhua Gao
1,2
1
Indiana University School of Medicine, Anatomy and Cell Biology,
Indianapolis, USA
2
Indiana University School of Medicine, Spinal Cord and Brain Injury
Research Group, Indianapolis, USA
Homeostatic synaptic plasticity has been proposed to underlie ac-
quired epileptogenesis. This hypothesis suggests that loss of neuronal
activity following brain injury will initiate epileptogenesis while
stimulating neuronal activity may prevent it. However, whether
stimulating neuronal activity can prevent posttraumatic epileptogen-
esis has not been directly tested. In the partially isolated neocortex
model of posttraumatic epileptogenesis (undercut) in mice, we made
patch clamp recording from cortical layer V pyramidal neurons and
found that spontaneous action potential firings in these neurons were
significantly reduced at both 1 and 7 days after injury. The frequencies
of both spontaneous excitatory and inhibitory synaptic currents
(sEPSCs and sIPSCs) were also significantly depressed but without
significant changes in the amplitudes of these events. In Thy1-chan-
nelrhodopsin-2 (ChR2) transgenic mice that express ChR2 in cortical
layer V pyramidal neurons, we made undercut injury and applied
optogenetic stimulation of the injured cortex using LED light for 7
days
in vivo
. Chronic optogenetic stimulation resulted in increased
seizure threshold as indicated by a higher drug dosage required for
inducing seizure and a longer latency period in pentylenetetrazol
(PTZ) test, and reduced cortical hyperexcitability as indicated by
decreases in the percentages of slices and mice in which epileptiform
activity could be evoked in field potential recording. The frequencies
of both sEPSCs and sIPSCs in neurons after optogenetic stimulation
were significantly lower that the control undercut mice. The results
support that homeostatic plasticity plays a role in the posttraumatic
epileptogenesis and that stimulating activity of cortical excitatory
neurons has prophylactic effect on posttraumatic epileptogenesis.
Keywords: Homeostatic plasticity, Optogenetic, Posttraumatic
epileptogenesis, Cerebral cortex
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
1,2
, D. Kacy Cullen
1,2
,
John Wolf
1,2
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
interrogate 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 (
<
15 min), yet exhibited axonal pa-
thology. Limitations of electrophysiological recording under anes-
thesia have led us to develop a chronic hippocampal electrode
implantation model in the awake, freely moving swine, allowing ex-
amination 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 rec-
ognition task for swine, a behavior known to be hippocampal de-
pendent. Pigs were trained on this task prior to electrode implantation.
Preliminary behavioral results indicate that sham injured swine reli-
ably 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 pro-
minent peak in hippocampal theta rhythm power in the freely be-
having pig with positive shifts in peak frequency and peak power
during periods of locomotion. 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 electrophysiological recordings with concurrent behav-
ior 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 neuro-
modulatory 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
A-10