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C1-13
DOSE-RESPONSE EVALUATION OF KOLLIDON IN THE
MIAMI FLUID PERCUSSION MODEL OF TRAUMATIC
BRAIN INJURY: AN OBTT CONSORTIUM STUDY
Helen Bramlett
1,2
, Ofelia Furones-Alonso
2
, David Sequiera
2
,
William Moreno
2
, Jessie Truettner
2
, W. Dalton Dietrich
1,2
1
University of Miami Miller School of Medicine, Neurological Sur-
gery, Miami, USA
2
University of Miami Miller School of Medicine, Miami Project to
Cure Paralysis, Miami, USA
Kollidon (VA64) is a compound with several potential mechanisms
useful in treating traumatic brain injury (TBI). Published reports
have shown that VA64 reseals membranes, reduces blood brain
barrier breakdown and necrosis as well as reducing motor deficits.
Male Sprague-Dawley rats were anesthetized and underwent mod-
erate fluid percussion (FP; 1.8–2.1 atm) TBI or sham surgery. Rats
were randomized into three treatment groups and administered
VA64 (0.2 g or 0.4 g/5 ml IV) or vehicle. Animal groups were TBI-
VA64-Low (n
=
15), TBI-VA64-High (n
=
15), TBI-Veh (n
=
15) or
Sham (n
=
15). Rats were tested on day 7 post-injury for sensori-
motor function (gridwalk, cylinder task). On days 13–21, rats were
assessed for cognitive function utilizing the simple place task, probe
trial and working memory task. On day 21, brain tissue was pro-
cessed for histology. One-way ANOVA was not significant for the
cylinder task (p
<
0.05) but was for the left forelimb of the gridwalk
task (p
<
0.05). Both dosages worsened outcome on this task com-
pared to TBI-Veh. For the hidden platform task, two-way repeated
measures ANOVA for latency was significant for group (p
<
0.05)
but not for group x day. However, neither dosage improved function
on this task compared to TBI-Veh. There was no significant differ-
ence between groups for the probe trial. Repeated measures ANOVA
for working memory latency was significant for trial (p
<
0.001), but
not group or group x trial. Histopathological analysis is currently
being assessed. We conclude that treatment with either dosage of
VA64 after FP did not improve sensorimotor or cognitive function.
In fact, left forelimb footfaults were increased with this drug. At this
time, although histology and biomarker data are still pending, be-
havioral findings of VA64 treatment in the FPI model in rats do not
support its further testing in OBTT. Support: US Army W81XWH-
10-1-0623.
Keywords: Kollidon, OBTT, fluid percussion
C1-14
PERSISTENT BEHAVIORAL DEFICITS IN RATS AFTER
MODERATE FLUID-PERCUSSION INJURY
Kathia Johnson
, Maggie Parsley, Ian Bolding, Donald Prough,
Douglas DeWitt, Stacy Sell
University of Texas Medical Branch, Anesthesiology, Galveston, USA
Background:
Although traumatic brain injury (TBI) is beginning to
be viewed as a chronic disease, few rodent studies have investigated
the long-term behavioral deficits elicited by well-established rodent
models of injury. The data presented here are an initial demonstra-
tion of which behavioral measures, commonly used in TBI research,
provide useful indications of long-term effects of brain injury in
rodents.
Methods:
Male Sprague-Dawley rats (250–300 g) were acclima-
tized to handling and pre-trained to vestibulomotor tasks and neuro-
logical testing prior to receiving moderate fluid-percussion-injury
(FPI) or sham-injury under general anesthesia. Rats were subjected to
simple reflex tests (Neuroscore) as well as beam-balance and beam-
walking tasks for 3 days immediately post injury. Rats were kept pair-
housed, handled and weighed twice weekly and then retested either 3
or 6 months after injury on the same tasks followed by a working
memory version of the Morris water maze.
Results:
On post-injury days 1 – 3, Two-factor ANOVA revealed
significant effects of injury on Neuroscore, Beam-Balance, and Beam-
Walk (
P
<
0.001), a significant effect of time (
P
<
0.001), and a sig-
nificant interaction (
P
<
0.001). At 3 and 6 months post-injury, there
were no significant differences between injured and sham rats in the
Beam-Balance or Beam-Walk tasks. However, a significant effect of
injury on Neuroscore persisted at both 3 (
P
<
0.01) and 6 months
(
P
<
0.05) as well as on the working memory test at 3 (
P
<
0.001) and
6 (
P
<
0.001) months post injury.
Conclusions:
These data suggest that vestibulomotor and coordi-
nation function recover within 3 months of a moderate injury, while
neurological and cognitive deficits persist out to 6 months after injury.
Therefore reflex testing and working memory water maze are useful
measures of behavioral deficits that persist after injury.
Support:
These studies were completed as part of an interdisci-
plinary research team funded by The Moody Project for Translational
Traumatic Brain Injury Research.
Keywords: Traumatic Brain Injury, Behavior, Morris Water Maze,
behavioral assessments
C2 Poster Session V - Group C: Gene Expression
C2-01
MENINGEAL INJURY DETECTED BY CONTRAST EN-
HANCED FLUID-ATTENUATED INVERSION RECOVERY
IMAGES AND DIFFERENTIAL GENE EXPRESSION
Jessica Gill
1
, Whitney Livingston
1
, Lawrence Lawrence
2
1
National Institutes of Nursing Research, Tissue Injury Branch, Be-
thesda, USA
2
National Institute of Neurological Disorders and Stroke, Stroke Di-
agnostics and Therapeutics Section, Bethesda, USA
Injury to the meninges is concomitant with TBI. In subjects who
sustained a meningeal injury, the highly sensitive fluid-attenuated
inversion recovery (FLAIR) MRI following gadolinium contrast ad-
ministration reveals enhancement of the meninges, an image that
standard scans cannot capture. The pathogenesis of this so called
traumatic meningeal injury (TMI) is not yet understood. By com-
paring gene expression data from head injured subjects with isolated
TMI, to similar subjects that are imaging negative, we hope to identify
pathways specific to meningeal injury and resulting secondary dam-
age. All subjects received a standard research MRI, contrast enhanced
FLAIR scan, and blood sample collection within 48 hours of injury.
Two groups of subjects were included, those; i) without any imaging
abnormalities (TMI-) and ii) with enhancement of the meninges on
post contrast FLAIR (TMI
+
) but with no other imaging abnormality.
Groups were compared on microarray gene expression using periph-
eral samples of blood. Extracted RNA was analyzed using GeneChip
3
¢
IVT Expression kit and Affymetrix. Partek Genomics Suite soft-
ware was used to compare gene expression. Forty subjects were in-
cluded, 23 participants in the TMI- group, and 17 participants in the
TMI
+
group. Loss of consciousness occurred in 27 participants, and
25 had posttraumatic amnesia. TMI was seen most frequently in the
falx (n
=
15). We observed 77 genes that were differentially expressed
in the TMI
+
group compared to the TMI- group, of which have
been previously associated with initiating inflammatory mediators,
A-76