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B1 Poster Session III - Group B: Aging
B1-01
DECOMPRESSIVE CRANIECTOMY IN CONJUNCTION
WITH LESION EVACUATION IN GERIATRIC TRAUMATIC
BRAIN INJURY: A PROPENSITY SCORE ANALYSIS
Takahiro Kinoshita
1,2
, Takeyuki Kiguchi
1
, Kazuhisa Yoshiya
3
,
Yasunori Fujimoto
2
, Ryuichiro Kajikawa
2
, Masahiko Hara
4
,
Akatsuki Wakayama
2
, Satoshi Fujimi
1
1
Osaka General Medical Center, Department of Emergency and
Critical Care, Osaka, Japan
2
Osaka Neurological Institute, Department of Neurosurgery, Toyo-
naka, Japan
3
Osaka University Graduate School of Medicine, Department of
Traumatology and Acute Critical Medicine, Suita, Japan
4
Osaka University Graduate School of Medicine, Department of
Cardiovascular Medicine, Suita, Japan
When it comes to evacuating intracranial hemorrhagic lesions in pa-
tients with traumatic brain injury (TBI), neurosurgeons perform either a
craniotomy or a decompressive craniectomy (DC). The aim of the
present study was to estimate the impact of DC on outcomes in elderly
patients. This retrospective cohort study, conducted in an institute that
specializes in neurosurgery in Japan from April 2009 to June 2014,
included 91 consecutive patients with TBI (aged 60 years or over) who
underwent evacuation of intracranial hemorrhagic lesions. Patients were
divided into two groups: craniotomy only or DC. We set the primary
endpoint as an unfavorable outcome (death or vegetative state), as
evaluated on the Glasgow Outcome Scale at 6 months after injury. The
secondary endpoints included existence of delayed hemorrhage and
occurrence of hydrocephalus requiring shunt placement. The inverse
probability of treatment weighting (IPTW) method was used to develop
a propensity model to adjust for baseline imbalances between groups.
The DC group exhibited greater severity both in clinical and computed
tomography findings according to baseline characteristics. After ad-
justing for these differences by IPTW using the propensity score, DC
was significantly associated with unfavorable outcomes (adjusted odds
ratio [OR], 8.00; 95% confidential interval [CI], 2.30–27.84;
p
=
0.002)
and delayed hemorrhage (adjusted OR, 13.42; 95% CI, 1.52–118.89;
p
=
0.022). There was no significant difference in the occurrence of
hydrocephalus requiring shunt placement. Our study showed that DC in
conjunction with evacuation of intracranial hemorrhagic lesions was
associated with worse functional outcome in elderly patients with TBI.
Keywords: decompressive craniectomy, Glasgow outcome scale,
delayed hemorrhage, elderly, propensity score, inverse probability of
treatment weighting
B1-02
THE ROLE OF TAU AND OTHER PATHOLOGIES IN AN
ANIMAL MODEL OF REPETITIVE MTBI
Benoit Mouzon
1,2
, Scott Ferguson
1,2
, Joseph Olubunmi
1
, Cillian
Lynch
1
, Corbin Bachmeier
1,2
, Fiona Crawford
1,2
1
Roskamp Institute, Pathology, Sarasota, USA
2
James A. Haley Veterans’ Hospital, Pathology, Tampa, USA
The Chronic Effects of Neurotrauma Consortium or CENC is dedicated
to understanding the chronic sequelae associated with neurotrauma,
primarily focused on mild TBI (mTBI)/concussion incurred by U.S.
service personnel. However, little is known about the timeline and se-
quence in which tau is processed following TBI, nor about the rela-
tionship with other TBI-dependent neuropathologies such as
neuroinflammation and cerebrovascular changes. This study is evalu-
ating tau alterations and accompanying neuropathologies over time after
r-mTBI in hTau transgenic mice. hTau mice aged either 8–12 weeks
will receive either r-mTBI or r-sham in order to control for effects of
repeated anesthesia. Mice will be euthanized for neuropathological,
genomic and biochemical analyses at 24 hrs, 5, 10 and 15 days, 3, 6 and
12 months after last mTBI/anesthesia. For the 15 day and 3, 6 and 12
month time points post injury mice will undergo a battery of neuro-
behavioral test in the 2 weeks immediately prior to euthanasia. The
entire paradigm is being replicated in hTau mice aged 12 months at the
time of injury, to study the effects of age at time of injury. r-mTBI in the
young cohort shows learning impairment post injury that progressively
worsens from 2 weeks to 12 months. To date, Tau IHC and ELISA
results suggest that r-mTBI is associated with a transient injury de-
pendent increase in p-tau accumulation with greater dendritic and
membranous staining in the cerebral cortex beneath the impact site
without neurofibrillary tangles. While a trend for an increase in ag-
gregated tau at 12 months post injury was observed, r-mTBI was not
associated with elevated brain levels of abnormal soluble tau phos-
phorylation. This study is ongoing and will take several years to
complete; our previous data suggest that neuroinflammatory pathology
is key in this model and that TBI-dependent tau pathology will be
evident in the older mouse models where tau pathology already exists.
Keywords: Tau, repetitive mTBI, inflammation, animal model
B1-03
CHRONIC IMPAIRMENT OF CEREBRAL BLOOD FLOW IN
A MOUSE MODEL OF REPETITIVE MILD TRAUMATIC
BRAIN INJURY
Cillian Lynch
1,2
, Corbin Bachmeier
1,2
, Benoit Mouzon
1,2
, Fiona
Crawford
1,2
1
The Roskamp Institute, Neuroscience, Sarasota, USA
2
James A. Haley Veteran Hospital, Pathology, Tampa, USA
Repeated exposure to mild traumatic brain injury (mTBI), as seen in
contact sports injuries, is known to predispose individuals to develop-
ment of neurodegenerative diseases such as Alzheimer’s Disease and
Chronic Traumatic Encephalopathy (CTE). CTE is characterized by
deposition and hyper-phosphorylation of the microtubule-associated
protein tau throughout the brain. In addition to aberrant proteinopathy,
neurodegenerative diseases are often associated with cerebrovascular
abnormalities, including changes in cerebral blood flow (CBF), and
loss of Blood Brain Barrier (BBB) integrity. Owing to the prevalence
of mTBI, there is an urgent requirement for animal models recapitu-
lating the pathological hallmarks, cognitive deficits, and cerebrovas-
cular components of neurodegeneration following repetitive mild head
trauma. We used heterozygous transgenic hTau mice expressing all 6
isoforms of human tau on a null murine tau background, allowing for
a clinically relevant investigation of the effects of repetitive mTBI (r-
mTBI) on cerebrovascular mechanics in the presence of human tau.
The closed-head mTBI was administered to mice under isofluorane
anesthetic using a 5 mm blunt metal impactor tip at a velocity of 5 m/s
and a strike depth of 1 mm, positioned midway to the sagittal suture.
We administered 2 hits every week for 3 months to replicate the
incidence of mTBI that can occur over the course of a career in
contact sports. We measured CBF in both hTau and wild-type mice 3
months and 7 months post-injury, respectively, using laser Doppler
imaging. We observed a significant decrease in CBF in wild-type mice
(10.66%
–
1.44% compared to sham) and hTau mice (8.92%
–
1.39%
compared to sham) This effect of r-mTBI on CBF may provide ra-
tionale for the link between head trauma and the development of
neurodegenerative disorders like CTE. We will continue to evaluate
A-43