156 / 198
Keywords: Glibenclamide, traumatic brain injury, cognitive and
motor outcomes, neuropathologic outcomes, controlled cortical
impact
D8-19
EVALUATION OF KOLLIDON VA-64 IN THE CONTROLLED
CORTICAL IMPACT MODEL OF TRAUMATIC BRAIN IN-
JURY: AN OBTT CONSORTIUM STUDY
Nicole Osier
2,3
, Hong Q. Yan
1,3
, Xiecheng Ma
1,3
, Stefania Mondello
5
,
Philip Empey
4
, Samuel Poloyac
4
, Keri Feldman
6,3
, Kevin Wang
8
,
Ronald Hayes
5
, Patrick M. Kochanek
6,3
,
C. Edward Dixon
1,7
1
UPitt, Neurosurgery, Pittsburgh, USA
2
UPitt, SON, Pittsburgh, USA
3
UPitt, SCRR, Pittsburgh, USA
4
UPitt, Pharmacy, Pittsburgh, USA
5
Banyan Biomarker, LLC, N/A, Alachua, USA
6
UPitt, CCM, Pittsburgh, USA
7
VA Pittsburgh Healthcare System, N/A, Pittsburgh, USA
8
University of Florida, Medicine, Gainesville, USA
Introduction:
Kollidon VA-64 is an excipient which reduces cellular
degeneration, edema, blood-brain-barrier damage, and motor deficits
after experimental TBI. We tested a single 15 min post-injury intra-
venous infusion of VA-64 on neurobehavioral and histopathological
outcomes after CCI.
Methods:
40 adult male Sprague Dawley rats were prepared for
CCI (4 m/sec, 2.7 mm deformation) or sham. Rats were randomized
into four groups: CCI
+
vehicle, CCI
+
low-dose VA-64, CCI
+
high-
dose VA-64, and Sham. Treatment was administered intravenously
over 5 min starting 15 min post-injury. Functional outcomes were
tested via Beam Balance Task (BBT) (days 1–5), Morris water maze
(MWM) acquisition (days 14–18) and probe trial (day 18). Rats were
sacrificed on day 21 for brain tissue volume analysis.
Results:
Groups differed on BBT performance (p
=
0.004); post hoc
testing revealed sham animals balanced longer than vehicle
(p
=
0.021) and high-dose (p
=
0.004) rats but not low-dose rats
(p
=
0.190). MWM acquisition latency differed by group (p
=
0.004);
post hoc testing revealed longer latencies (vs. sham) in the
CCI
+
vehicle (p
=
0.015) and CCI
+
high-dose group (p
=
0.004) but
not CCI
+
low-dose group (p
=
0.104). No group differences existed on
probe trial. There was no treatment effect of Kollidon VA-64 vs.
vehicle on BBT or MWM. Lesion volume and hemispheric volume
loss were unaffected by treatment.
Conclusions:
Administration of low-dose Kollidon VA-64 produced
intermediate benefit on BBT and MWM in the CCI model within the
rigors of our OBTT assessment paradigm. Low-dose Kollidon VA-64
may merit additional study in CCI depending on the pending biomarker
assessments; however, overall effects were modest.
Acknowledgments
United States Army (W81XWH-10-1-0623).
Keywords: traumatic brain injury, neuroprotection, consortium, rat
D8-20
TAU OLIGOMER SPECIFIC MONOCLONAL ANTIBODY TO
TREAT TRAUMATIC BRAIN INJURY
Bridget Hawkins
1
, Maggie Parsley
1
, Ian Bolding
1
, Yaping Zeng
1
,
Rakez Kayed
2
, Donald Prough
1
, Douglas DeWitt
1
1
University of Texas Medical Branch (UTMB), Department of An-
esthesiology, Galveston, USA
2
University of Texas Medical Branch (UTMB), Mitchell Center for
Neurodegenerative Diseases, Galveston, USA
Introduction:
Traumatic brain injury (TBI) causes nearly $50 billion
in medical expenses and lost productivity annually, making TBI one
of the major health care problems in the United States. TBI can also
predispose individuals to develop a pathologically distinct form of
tauopathy-related dementia at an early age. We gave a single dose of
anti-tau oligomer specific monoclonal antibodies (TOMA) after TBI
in rats and examined neuronal injury and vascular reactivity. TOMA
is unique in that it only recognizes oligomeric tau, a toxic form of the
microtubule protein tau, while leaving normal, functional tau protein
intact.
Methods:
Male Sprague-Dawley rats were anesthetized, intubated,
mechanically ventilated and prepared for fluid percussion injury (FPI).
Animals were randomly assigned to receive moderate (2.0 atm) FPI
with vehicle (Veh; n
=
6) or moderate FPI with TOMA (TOMA;
n
=
6). Return of righting reflex (RR) time measurements commenced
immediately upon injury. Animals were reanesthetized and 1 hour
post FPI they were given either vehicle or TOMA through an in-
tracerebroventricular (icv) injection. Animals survived for 24 hours
prior to being euthanized and their brains and middle cerebral arteries
(MCA) were collected. We sectioned (coronal, 10
l
m thickness) and
stained each brain with .001% Fluorojade-C (FJ), and blindly counted
FJ-positive cells in the CA1/2 and CA3 regions of the hippocampus.
We measured MCA diameter and vascular reactivity, blinded to the
treatment group.
Results:
We saw a statistically significant decrease (vs. Veh) in the
number of FJ
+
neurons in the TOMA-treated animals, suggesting a
possible therapeutic effect. We conclude from these data that TOMA
appears to have a beneficial effect on TBI animals, most likely by
binding to the toxic tau oligomers that accumulate after FPI.
These studies were completed as part of an interdisciplinary re-
search team funded by The Moody Project for Translational Trau-
matic Brain Injury Research.
Keywords: tau, therapeutic, antibody, fluid percussion injury
D8-21
THERAPEUTIC APPLICATION OF A PULSED LASER SYS-
TEM FOR BRAIN TRAUMA
Jutatip Guptarak
1
, Rinat Esenaliev
2
, Irene Petrov
2
, Yuriy Petrov
2
,
Debbie Boone
1
, Harris Weisz
1
, Margaret Parsley
1
, Stacy Sell
1
, Helen
Hellmich
1
, Donald Prough
1
,
Maria-Adelaide Micci
1
1
UTMB, Anesthesiology, Galveston, USA
2
UTMB, Center for Biomedical Engineering, Galveston, USA
Background:
We have developed a novel, non-invasive short-pulsed
laser system for the treatment of traumatic brain injury (TBI). Our
proprietary system combines both the benefits of near infrared laser
light (808 nm) and of ultrasound waves, which are generated with
each short (10 ns) high-energy (5 mJ) laser pulse within the tissue.
Methods:
Anesthetized, adult male Sprague-Dawley rats were
subjected to moderate blast-induced neurotrauma (BINT) using the
Vandenberg device.
S
hort
P
ulsed
L
aser
T
herapy (
SPLT
) was applied
transcranially 1 hour after BINT for 5 minutes. Comparisons were
performed between SPL-treated rats, rats subjected to BINT but not
treated and SHAM controls (rats anesthetized for the same amount of
time as the injured rats but not subjected to BINT). Vestibulomotor
function was assessed on post-injury days (PID) 1–3 on the beam
balance and beam walking tasks. Cognitive function was assessed on
PID 6–10 using a working memory water maze test. BDNF and
A-120