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B3-14
BIOMECHANICAL RESPONSE, NEUROPATHOLOGY AND
BIOMARKER EXPRESSION IN AN EXPERIMENTAL MODEL
OF TRAUMATIC BRAIN INJURY
Liying Zhang
, John Cavanaugh, Yan Li, Srinivas Kallakuri
Wayne State University, Biomedical Engineering, Detroit, USA
There is a lack of traumatic brain injury models that correlate mea-
sured biomechanical response, neuropathology and levels of bio-
markers that reflect the severity of brain injury. This study uses a head
impact model which correlates quantified biomechanics to axonal
histology, and serum and CSF biomarker expression in determining
TBI severity. Anesthetized male Sprague-Dawley rats were subjected
to TBI using a head impact device from 1.25, 1.75 and 2.25 m drop
heights. Linear and angular head kinematics were measured with
miniature transducers. Twenty-four hours post-trauma, CSF and blood
were collected and levels of amyloid beta (A
b
)1-42, neurofilament H
(NF-H), glial fibrillary acid protein (GFAP) and interleukin (IL-6)
were assessed by ELISA. Traumatic axonal injury (TAI) was quan-
tified as the total number of
b
-APP-reactive axonal swellings/retrac-
tion balls in the corpus callosum (CC) and pyramidal tract (Py).
Compared to controls, significantly higher CSF and serum NF-H
levels were observed, except in 1.25 m-group in serum. CSF and se-
rum NF-H levels at 2.25 m were significantly higher than at other
heights, and CSF and serum NF-H levels at 1.75 m were significantly
higher than at 1.25 m. In both CSF and serum, GFAP levels were
significantly higher at 2.25 m than other groups/controls. GFAP levels
at 1.75 m and 1.25 m were significantly higher than in controls. TBI
rats also showed significantly higher levels of IL-6 versus control. A
b
levels were not different among impact groups/controls. CSF GFAP
was the best single biomarker (AUC
=
0.946) followed by CSF NF-H
(AUC
=
0.938). Serum GFAP (AUC
=
0.920) and NF-H (AUC
=
0.85)
had better predictive abilities than the others. Correlations between
biomechanical parameters, biomarker levels, and TAI numbers in-
dicated that NF-H and GFAP in CSF and serum were reliable pre-
dictors for severe TBI in this model, whereas CSF NF-H and CSF
and serum GFAP were good indicators for mild TBI. Both CSF and
serum NF-H correlated well with quantified TAI in CC and Py,
suggesting they are directly related to the severity of the mechanical
trauma to the brain.
Keywords: rodent impact head injury, biomechanical measure-
ments, axonal pathology, serum and CSF biomarker
B3-15 (See D8-01)
NECK STRENGTH IS ASSOCIATED WITH HISTORY OF
CONCUSSION IN AMATEUR ADULT SOCCER PLAYERS
Eva Catenaccio
B4 Poster Session III - Group B: Epilepsy/Seizure
B4-01
PROGRESSIVE SEIZURES FOLLOWING MICROGLIAL
ACTIVATION AND INFLUX OF PROFESSIONAL APCS IN
AUTOIMMUNE TARGETING OF ASTROCYTES
Yelena Grinberg
1
, Bruno Meza Lo´pez-Bayghen
2
, Devin K. Binder
1
,
David D. Lo
1
, Corinne C. Ploix
1
, Monica J. Carson
1
1
University of California, Riverside, Biomedical Sciences; Center for
Glial-Neuronal Interactions, Riverside, USA
2
CINVESTAV, Toxicology, Mexico City, Mexico
Brain injury-related inflammation results in increased susceptibility
to seizures and epilepsy, as well as migraine. Innate immune sig-
naling, including proinflammatory cytokine modulation of astro-
cytic function, has been implicated in epileptogenesis. Far less is
known about the role of adaptive immunity, although T cells have
been found in brain tissue of both epilepsy patients and experi-
mental animals following seizure. To determine whether an anti-
gen-driven response against a non-neuronal target can be sufficient
to initiate epilepsy, we generated mice with CD4 T cells targeted
against an astrocyte-expressed molecule. Following adjuvant
stimulation, animals developed visually overt seizures. We looked
at the progression of events leading up to seizures to find: 1)
progressive infiltration of macrophages and B cells; 2) infiltration
of IFN
c
-producing T cells throughout brain; 3) progressive acti-
vation of microglia; 4) astrogliosis. Unlike brain-infiltrating antigen
presenting cells (APCs), microglia expressed low levels of mole-
cules regulating T cell activation, phagocytosis, and inflammatory
responses, but upregulated many of these molecules over the
course of disease progression. This suggests that microglia may be
more plastic and are able to progressively become highly activated,
providing a greater contribution to inflammatory signaling and
regulation of T cell responses later into epileptogenesis. However,
APCs appear to have a greater capacity to phagocytose and pro-
duce inflammatory responses, and thus are likely the determinants
of disease initiation. Here we show that autoimmune targeting of
astrocytes, and not neurons, can result in progressive seizures.
Using this model, we can manipulate the contribution of distinct
immune cell types to progression of epileptogenesis. For example,
to determine whether eliminating T cells or B cells after seizures
develop can 1) halt or reverse disease progression, 2) not affect
seizure progression once adaptive immunity-mediated initiating
events have occurred, or 3) alternatively, whether T cells become
protective in later stages of disease.
Keywords: microglia, T cell, macrophage, adaptive immunity
B4-02
NEURONAL GLUTAMATE TRANSPORTER GENETIC VAR-
IATION: IMPACT ON EPILEPTOGENESIS AND EPILEPSY
RISK FOLLOWING SEVERE TBI
Anne Ritter
1,2
, Candace Kammerer
3
, Yvette Conley
4,5
, Amy
Wagner
2,5,6
1
Univ Pittsburgh, Epidemiology, Pittsburgh, USA
2
Univ Pittsburgh, PhysicalMed/Rehab, Pittsburgh, USA
3
Univ Pittsburgh, Human Genetics, Pittsburgh, USA
4
Univ Pittsburgh, Health Promotion, Pittsburgh, USA
5
Univ Pittsburgh, Safar Center, Pittsburgh, USA
6
Univ Pittsburgh, Neuroscience, Pittsburgh, USA
Post-traumatic seizure (PTS) is a well-recognized complication fol-
lowing severe traumatic brain injury (sTBI). Risk factors for PTS have
been identified, but there remains variability in predicting who will
develop PTS. Secondary injury cascades like excitotoxicity may in-
fluence epileptogenesis following sTBI. Glutamate transporters man-
age glutamate levels and excitatory neurotransmission physiologically
and can be disrupted in both epilepsy and TBI. We hypothesized
genetic variation in neuronal glutamate transporter genes would be
significantly associated with epileptogenesis and increased PTS risk
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