Page 148 - NNS 2014 Program & Abstract Book

Seven days post injury, spontaneous RGC activity was slightly
increased, while the median amplitude of responses to light OFF-set
increased significantly with decreased response duration.
Five weeks post injury, spontaneous activity, the median ON re-
sponse amplitude and response duration, and the OFF response am-
plitude were all significantly increased.
Four months post injury all measures of RGC physiology had re-
covered to near-normal values. Cell counts of the entire retina and
dendritic analysis revealed significantly decreased RGC number and
abnormal dendritic fields, which correlated with abnormal RGC re-
ceptive fields observed with MEA.
TBI induces dramatic alterations in RGC physiology after an initial
period of relatively normal function. The return to normal RGC
function at later time points may reflect surviving RGC subpopula-
tions that accommodated for a substantial loss of RGCs after injury. A
better understanding of RGC physiology after blast exposure will help
in the development of improved clinical testing and treatment of those
suffering from TBI.
Key words
retinal ganglion cell, vision
D2-09
OVERPRESSURE BLAST INJURY INDUCED STRUCTURAL
AND FUNCTIONAL CHANGES IN THE BRAIN AND BASI-
LAR ARTERY
Toklu, H.Z.1–3, Muller-Delp, J.2, Yang, Z.2, Oktay, S.2,3, Kirichenko,
N.1,2, Sakarya, Y.1,2, Llinas, K.1, Ghosh, P.2, Strang, K.2, Scarpace,
P.J.1, Wang, K.W.2, Tumer, N.1,2
1Geriatric Research Education & Clinical Center, Malcolm Randall
Veterans Affairs Medical Center, GAINESVILLE, United States
2University of Florida, GAINESVILLE, United States
3Marmara University, Istanbul, Turkey
Overpressure blast-induced brain injury (OBI) is a common problem
for military population. It leads to progressive pathophysiological
changes in brain. Therefore, we investigated the structure and function
of the basilar artery (BA) following OBI.
Male Sprague Dawley rats (250–300 g) were divided into Control
(Naive), single OBI [30 psi peak pressure, 1-2 ms duration], and re-
peated (every three days) OBI (r-OBI). Cortex and cerebellum tissues
were taken 24 h post injury. BA was cannulised in the pressurized
system and vascular responses to KCl, acetylcholine (ACh) and die-
thylamine (DEA)-NONO-ate evaluated.
Neurological status was impaired in OBI and r-OBI groups
(4.16 – 1.5, 3.71 – 1.4 respectively vs 0.66 – 0.5 in control). A signif-
icant increase (p < 0.05-0.001) was detected in malondialdehide – an
index for lipid peroxidation-levels in OBI and r-OBI groups in cortex
and cerebellum. A significant decrease was detected in glutathione
(GSH) levels in r-OBI compared with control group in cortex
(p < 0.01) and cerebellum (p < 0.05). Myeloperoxidase activity – an
index for neutrophil infiltration – was significantly (p < 0.01-0.05)
elevated in r-OBI. Additionally, tissue thromboplastic activity, a
marker for coagulation, was significantly increased in both regions,
indicating a tendency for bleeding. Edema and protein levels of NGF
and NFKB were significantly (p < 0.01) increased in cortex after r-
OBI. Furthermore, the GFAP and Iba1 immunoreactivity also dem-
onstrated cortical injury. Endothelin contractility was increased and
ACh relaxation was decreased in BA. However, impaired DEA-in-
duced dilation and increased wall thickness to lumen ratio were ob-
served only in the r-OBI.
Single OBI causes endothelium-dependent and -independent alter-
ations in BA function and structural changes in the artery wall. It may
be a result of the increased oxidative stress and concomitant decrease
in antioxidant levels.
Key words
basilar artery, blast injury, brain, vascular
D2-10
ABSTRACT TITLE AXONAL INJURY AND MICROGLIAL
ACTIVATION IN MICROPIGS FOLLOWING DIFFUSE
BRAIN INJURY: AN OBTT CONSORTIUM REPORT
Lafrenaye, A.D., Povlishock, J.T.
Department of Anatomy and Neurobiology, Virginia Commonwealth
University Medical Center, Richmond, VA
Traumatic brain injury (TBI) remains a major heath care concern.
Although our knowledge of the complex pathologies associated
with TBI has progressed and many therapeutics have shown
promising results in rodent models of TBI, this efficacy has been
limited when translated to humans. Due to this low success in hu-
man translation, there has recently been a call for the development
of higher order animal experimental models to better evaluate po-
tential therapeutics prior to clinical study. With this goal in mind we
have begun characterization of a central fluid percussion injury
(CFPI) model of mild diffuse TBI in the adult micro pig. Assess-
ment of diffuse axonal injury (DAI) was achieved by computer
assisted counting of axonal profiles exhibiting accumulation of both
the C and N-terminus fragments of amyloid precursor protein
(APP). The proportion of morphologically altered activated Iba-
1 + microglia was also quantitatively analyzed using stereological
principals. In this model, macroscopic examination of the brain at
six hours post-TBI revealed no contusion or hematoma formation
and only minimal subarachnoid hemorrhage, consistent with mild
diffuse TBI. Analysis of multiple brain sites revealed DAI, which
was particularly abundant in the thalamus and corpus callosum, with
the numbers of damaged axons averaging 11.9 swellings/0.72 mm2
in the thalamus and 80 swellings/0.72 mm2 in the corpus callosum.
Activated microglia were primarily identified in areas associated
with DAI, with the suggestion that these cellular responses are
linked. The consistent spatial and temporal features of DAI in this
animal model are reminiscent of those seen in humans, suggesting
that this constitutes an excellent animal model for future drug and
biomarker screening. This work was performed as a component of
the Operation Brain Trauma Therapy consortium, which is sup-
ported by the US Army grant W81XWH-10-1-0623.
Key words
immunocytochemistry, microglia, micropig, ultrastructure
D2-11
CHARACTERIZATION OF A BLAST-INDUCED BRAIN AND
EYE INJURY MODEL IN RATS
Sharrow, K.M.1, DeMar, J.C.2, Hill, M.I.2, Edwards, A.A.2, Long,
J.B.2, Oliver, T.G.1
1Department of Clinical Pharmacology and Translational Medicine
Walter Reed Army Institute of Research, Silver Spring, MD, USA
2Blast-Induced Neurotrauma Branch Walter Reed Army Institute of
Research, Silver Spring, MD, USA
A-116