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a clinical setting. Li and VAP robustly improved neurological re-
covery when given soon in this model that mimics a ploytraumatic
clinical situation.
Keywords: Hypotension, Lithium, Valproate, Mild Traumatic Brain
D8-05
LOWERING TUMOR NECROSIS FACTOR-
a
SYNTHESIS
AMELIORATES NEURONAL AND COGNITIVE LOSS
AFTER MILD TRAUMATIC BRAIN INJURY IN MICE
Barry Hoffer
1
, Alan Hoffer
1
, Renana Baratz
2
, Chaim Pick
2
, Nigel
Greig
3
1
Case Western Reserve University, Neurosurgery, Cleveland, USA
2
Sackler School of Medicine, Tel-Aviv University, Anatomy, Tel Aviv,
Israel
3
National Institute on Aging, National Institutes of Health, Drug
Design & Development Section, Baltimore, USA
Treatment of traumatic brain injury (TBI) represents an unmet medical
need, as no effective pharmacological treatment currently exists. De-
velopment of such a treatment requires a fundamental understanding of
the pathophysiological mechanisms that underpin the sequelae resulting
from TBI, particularly the ensuing neuronal cell death and cognitive
impairments. Tumor necrosis factor-alpha (TNF-a) is a cytokine that is
a master regulator of systemic and neuro inflammatory processes. TNF-
a levels are reported rapidly elevated post TBI and, potentially, can lead
to secondary neuronal damage. To evaluate the role of TNF-a in TBI,
particularly as a drug target, the present study evaluated time-dependent
TNF-a levels in brain in a mouse closed head 50 g weight-drop mild
TBI (mTBI) model in the presence and absence of post-treatment with
an experimental TNF-a synthesis inhibitor, 3,6’-dithiothalidomide.
Brain TNF-
a
levels peaked at 12 hr post injury, and returned to baseline
by 18 hr. This was accompanied by neuronal loss and an increase in
astrocyte number (evaluated by NeuN and GFAP immunostaining re-
spectively), as well as an elevation in the apoptotic death marker BID
at 72 hr. Impairments in measures of cognition, evaluated by novel
object recognition and passive avoidance paradigms, were evident at 7
days after injury. Treatment with the TNF-
a
synthesis inhibitor 3,6’-
dithiothalidomide 1 hr post injury prevented the mTBI-induced TNF-
a
elevation and ameliorated the neuronal loss (NeuN), elevations in as-
trocyte number (GFAP) and BID, and cognitive impairments. Cognitive
impairments were prevented by treatment as late as 12 hr post mTBI,
but were not reversed when treatment was delayed until 18 hr. These
results suggest that pharmacologically limiting the generation of TNF-
a
post mTBI may mitigate secondary damage and define a time window
of up to 12 hr to achieve this reversal.
Keywords: Neuroprotection, Inflammation, Neurodegeneration,
Cognition
D8-06
BIODEGRADABLE NEURO-SPINAL SCAFFOLD PRE-
SERVES SPINAL CORD ARCHITECTURE FOLLOWING
SPINAL CONTUSION INJURY IN RATS
Richard Layer
, Alex Aimetti, Pamela Podell, Simon Moore, Thomas
Ulich
InVivo Therapeutics, Research, Cambridge, USA
Severe spinal cord injury (SCI) is accompanied by disruption of
spinal cord architecture, including cystic cavitation and tissue loss.
We hypothesized that implantation of a biodegradable, biomaterial
scaffold into the injured spinal cord could serve as a locus for ap-
positional healing and tissue remodeling that would preserve spinal
cord architecture. We evaluated the effect of implantation of scaf-
folds composed of a block copolymer of poly(lactic-co-glycolic
acid) and poly(L-lysine) (PLGA-PLL) on preservation of spinal ar-
chitecture in a rat contusion model of severe spinal cord injury
(SCI). A spinal T10 contusion injury was created in female Sprague-
Dawley rats with a Precision Systems IH Impactor (220 kDyn).
Cylindrical scaffolds (1.0 mm diameter, 2.0 mm length) were surgi-
cally implanted at the lesion site between 24 and 72 hours later.
Body weight, development of mechanical allodynia, and recovery of
coordinated hind limb function using the Basso, Beattie, and Bres-
nahan (BBB) scale were evaluated for 12 weeks. Spinal architecture
was evaluated at 12 weeks by morphometric analysis of parafor-
maldehyde fixed frozen sections (20
l
m) stained with hematoxylin &
eosin (H&E). Scaffold implantation did not result in mechanical
allodynia, did not impair body weight gain, and did not interfere with
partial recovery from full hind-limb paralysis. Histological analysis
revealed that rats in the non-treated control group developed large
cavities surrounded by a rim of spared tissue. In contrast, in rats
treated with scaffold implantation surgery, cavity volume decreased
by 86% and spared tissue width increased by 44%. Although scaf-
folds were fully resorbed by 12 weeks after implantation, the amount
of remodeled tissue at the site of implantation in the lesion epicenter
increased by 111%. These results demonstrate that PLGA-PLL
scaffold implantation in the acutely injured spinal cord can reduce
cavitation, promote tissue sparing and remodeling, and act as a locus
for appositional healing. Scaffold implantation preserves spinal cord
architecture and may play an important role in combinatorial spinal
cord repair strategies.
Keywords: biomaterial, tissue engineering, scaffold, implantation,
biodegradable
D8-07
HYPERTONIC SALINE THERAPY AND DECOMPRESSIVE
SURGERY WITH MULTI-MODAL THERAPY IN ACUTE
SPINAL CORD INJURY
George Hanna
1
, Olaide Ajayi
1
, Nam Yoon
1
, Farbod Asgarzadie
1
,
Huitzilin Olmecah
2
1
Loma Linda University Health, Department of Neurological Surgery,
Loma Linda, USA
2
Loma Linda University Health, Neurosciences Intensive Care Unit,
Loma Linda, USA
Acute spinal cord injury is a debilitating condition that has signifi-
cant associated morbidity and mortality that has progressed to be-
coming a chronic medical condition with an estimated prevalence of
about 270,000 individuals and with an incidence of 12,000 new cases
each year in the United States. The majority of spinal cord injury
cases are secondary to trauma and permanent neurological deficits
are believed to be due to secondary injury most significantly due to
compressive forces and edema. Despite advances in intensive care
and refinement of surgical approaches, there are currently no widely
accepted medical or surgical interventions for managing spinal cord
edema. Interestingly, however, there has been generally more liter-
ature and data on decreasing cerebral edema, including the admin-
istration of hypertonic saline. There have been several basic science
articles written on the proposed efficacy of hypertonic saline ad-
ministration in decreasing spinal cord edema after acute spinal
cord injury but no known clinical studies to date. A review of the
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