82 / 198
health problems who had sustained a ‘‘pure’’ MTBI. Of all patients
screened, 1,970 (65.2%) had a MTBI, 370 (12.2%) had a more severe
TBI, and 683 (22.6%) had a head trauma without signs of brain injury.
Injury-related and participant-related data were collected from hos-
pital records. We investigated the frequency of pre-injury diseases and
conditions in the population and the effect of applying different in-
clusion/exclusion criteria on patient enrollment.
Results:
The most common pre-injury diseases were circulatory
(39.4–47.0%), neurological (23.7–28.4%), and psychiatric (25.8–
27.7%) disorders. Alcohol abuse was present in 18.4–24.3%. The
most common medications were for cardiovascular (34.8–36.9%),
central nervous system (27.7–30.9%), and blood clotting and anemia
indications (21.5–24.6%). Of the screened patients, only 2.1% met all
the enrollment criteria. Age, neurological and psychiatric problems
were the most common reasons for exclusion.
Conclusions:
Most of the MTBI patients have some pre-injury
conditions or regular medication that could influence clinical out-
come. Excluding patients with pre-existing conditions creates a sig-
nificant selection bias.
Keywords: mild traumatic brain injury, comorbidity, patient re-
cruitment, CT imaging
B2 Poster Session III - Group B: Neurodegeneration
B2-01
THE ROLE OF APOPTOSIS IN LONG-TERM AXONAL, MI-
CROVASCULAR AND BLOOD-BRAIN BARRIER DAMAGE
AFTER TRAUMATIC BRAIN INJURY IN RATS
Olena Glushakova
, Andriy Glushakov, Ronald Hayes
Banyan Biomarkers, Inc., Banyan Laboratories, Alachua, USA
Introduction:
Acute and long-term disabilities associated with TBI
are mediated by multiple molecular and cellular pathobiological
cascades initiated by the acute traumatic event that potentially may
lead to chronic traumatic encephalopathy (CTE), Alzheimer’s disease
(AD) and other dementias. Data indicate that AD is associated with
caspase 3-mediated apoptosis, tau pathologies and abnormal angio-
genesis. The goal of this study is to evaluate microvascular abnor-
malities at acute and chronic stages following TBI in rats.
Methods:
TBI in adult rats was induced by controlled cortical
impact (CCI). Brain pathology was assessed at different time points
from 24h to 3 months following injury using immunohistochemistry
(IHC) on paraffin-embedded 6
l
m brain sections and examined for the
following biomarkers: cleaved caspase-3 (apoptosis), caspase cleaved
tau (truncated at Asp421) (neuronal cytoskeleton damage), SMI-71
(blood-brain barrier) and CD34 (endothelial and progenitor cells) and
CD68 (macrophages).
Results:
TBI resulted in increased level of cleaved caspase-3 in both
white and gray matter at the latest stages following injury. IHC staining
of cleaved caspase-3 was gradually increased over the 3 month duration
of the study in the corpus callosum and thalamus. These increased
levels of caspase-3 were associated with an increase in the levels of
microvascular, inflammatory and axonal damage markers predomi-
nantly in white matter. In corpus callosum, IHC with CD34 revealed
TBI-induced microvascular abnormalities which were characterized
by proliferation, irregular capillary formation and atypical structure
of the new vessels. Further, increased perivascular accumulation levels
of caspase cleaved Tau was observed at 2 and 3 month after injury.
In addition, fluorescent co-staining experiments demonstrated co-
localization of caspase-3 with SMI-71, and cleaved caspase-3 with CD68
suggesting involvement of apoptosis and delayed neuroinflammation in
the mechanisms of miscrovascular damage in corpus callosum.
Conclusions:
This study, for the first time, indicate that evolving
white and gray matter degeneration following experimental TBI is
associated with significantly delayed microvascular damage, abnor-
mal angiogenesis and perivascular Tau accumulation. Our results
suggest mechanisms underlying delayed apoptosis following TBI
which could provide novel insights into chronic pathological re-
sponses to TBI and potential common mechanisms underlying TBI
and neurodegenerative diseases.
Keywords: Cleaved caspase-3, chronic TBI, caspase cleaved Tau,
blood-brain barrier, CD34
B2-02
THE ROLE OF TREM2 IN TRAUMATIC BRAIN INJURY-
INDUCED NEUROINFLAMMATION AND NEURODEGEN-
ERATION
Maha Saber
, Olga Kokiko-Cochran, Ryan Teknipp, Bruce Lamb
LernerO˜ s research institute at Cleveland clinic, Neurosciences, Cle-
veland, USA
Traumatic brain injury (TBI) affects approximately 3.8 million people
annually and costs the US $48 million (NINDS). There is increasing
evidence that individuals exposed to TBI, have increased risk of the
development of multiple neurodegenerative conditions, including Alz-
heimer Disease (AD), Frontotemporal dementia, and chronic traumatic
encephalopathy (CTE). TBI triggers a potent neuroinflammatory re-
sponse characterized by astrogliosis, activation of microglia, infiltration
of peripheral monocytes, and increased synthesis and release of pro- and
anti-inflammatory molecules. Recent evidence suggests that alterations
in innate immunity may promote neurodegeneration. This includes ge-
netic studies demonstrating that heterozygous loss of function mutations
in
Triggering Receptor Expressed on Myeloid cells 2 (TREM2)
is asso-
ciated with a 3–4 fold higher risk for not only AD but multiple other
neurodegenerative diseases similarly to TBI. TREM2 is a transmem-
brane receptor expressed on innate immune cells that has canonically
been shown to negatively regulate Toll- Like receptor (TLR) signaling, a
major pathway in innate immunity and inflammation.
The hypothesis of
the current studies is that TREM2 deficiency will increase neuroin-
flammation and neurodegeneration following TBI and lead to long-term
cognitive deficits
. Currently, no work has been published on the role of
TREM2 in TBI. To examine the role of TREM2 in TBI-induced neu-
roinflammation and neurodegeneration, control mice were exposed to
experimental TBI and examined at early time points. Notably, there was a
substantial increase in TREM2
+
cells in close proximity to the injury
cavity and increased expression of TREM2 transcripts. TREM2 deficient
mice were then given TBI and Immunohistochemistry as well as bio-
chemistry was performed. These mice showed an altered inflammatory
response. Lastly, motor and cognitive behavioral test were preformed on
these mice. Though there are no motor deficits in these mice, there seems
to be a deficiency in performing other cognitive tests. Mice are currently
being aged to look at long-term aspects of TBI on TREM2 deficiency.
Keywords: TREM2, Macrophages, Transgenic mice, Alzheimer’s
Disease
B2-03
PROGRESSIVELIMBICANTEROGRADETRANS-NEURONAL
DEGENERATION (LATND): A NEUROPATHOLOGICAL BIO-
MARKER IN TBI-INDUCED CTE & DEMENTIA
William Torch
Neuro-Developmental & Neuro-Diagnostic, Washoe Sleep Disorders
Ctr, Reno, NV, USA
A-46