This is the first evidence of an increase in thrombin and activation
of the thrombin receptor PAR-1 in human epilepsy. Taken together,
the compromise of the BBB in chronic epilepsy, and expression of
PAR-1 on astrocytes are preliminary evidence in human of a role for
BBB injury and astrocyte-derived thrombin in the mechanisms of
epilepsy, including post-traumatic seizures.
Key words
astrocytes, BBB, epilepsy, PAR-1, thrombin
B4-25
FACILITY-LEVEL CHARACTERISTICS AND PEDIATRIC
IN-HOSPITAL MORTALITY FOLLOWING SEVERE TRAU-
MATIC BRAIN INJURY
Mills, B.M.
1,2
, Rowhani-Rahbar, A.
1,2
, Vavilala, M.S.
2
1
University of Washington, Department of Epidemiology, Seattle, USA
2
Harborview Injury Prevention and Research Center, Seattle, USA
To enhance understanding of how facilities may improve pediatric
traumatic brain injury (TBI) care and outcomes, we evaluated associa-
tions between facility characteristics and risk of 30-day in-hospital
mortality among severe pediatric TBI patients in the National Trauma
Data Bank from 2008 through 2012. Patients were included if they were
<
18 years of age at admission and stayed in the ICU for
2 days. Severe
TBI was defined as a total Glasgow Coma Scale score on admission of
<
9, a head Abbreviated Injury Scale score of
3, and an International
Classification of Diseases, Ninth Version code for TBI diagnosis (800.0-
801.9, 803.0-804.9, 850.0-854.1, 950.1-950.3, 959.01, or 995.55). Pa-
tients were excluded if they were missing discharge disposition or had a
total hospital stay of
£
2 days. Only Level I and II facilities were in-
cluded. A total of 12,880 patient records in 441 facilities were analyzed.
Multivariate Poisson regression models were used to calculate risk ratios
(RR) for mortality while accounting for clustering by facility. Patient-
level potential confounders included age, transfer status, hypotension and
pulse at admission, mechanism of injury, severity of injury and ventilator
use. Facility-level characteristics of interest included trauma center level,
teaching status, region, number of beds, non-profit status and presence of
pediatric trauma care. In the multivariate analysis, patients in the Mid-
west (RR
=
1.48; 95% confidence interval (CI): 1.24, 1.75), West
(RR
=
1.30; 95% CI: 1.08, 1.57), and South (RR
=
1.54; 95% CI: 1.32,
1.80) regions had a significantly higher risk of mortality (than those in the
Northeast region (referent group). Other facility-level characteristics
were not significantly associated with mortality. Significant regional
variation in pediatric severe TBI mortality persists even after accounting
for patient- and other facility-level characteristics.
Key words
epidemiology, facility chacracteristics, in-hospital mortality, severe
TBI
B4-26
THE JUVENILE RAT BRAIN SHOWS INCREASED VUL-
NERABILITY TO LOW IMPACT REPETITIVE INJURY
OVER PROLONGED POSTTRAUMATIC INTERVALS
Todani, M.
1,2
, Miyauchi, T.
1,2
, Wei, E.P.
1
, Povlishock, J.T.
1
1
Virginia Commonwealth University, Department of Anatomy and
Neurobiology, Richmond, USA
2
Yamaguchi University Hospital, Advanced Medical Emergency and
Critical Care Center, Ube, Japan
Emerging evidence suggests that the juvenile brain may be more
sensitive to TBI than the adult. Previously in adult rats, we have
reported that the damaging cerebrovascular and axonal conse-
quences of repetitive TBI were a function of both the injury in-
tensity as well as the interval between repetitive injuries. The aim
of the current study was to investigate if the threshold for repetitive
injury as well as the intervals needed to evoke the damaging con-
sequences of repetitive injury were reduced in juvenile rats. Fur-
ther, in these studies we also assessed the neuroprotective effects of
mild vs moderate hypothermia.
Seven and eight week juvenile rats were subjected to repetitive
mTBI of varying severity employing different time intervals between
the repetitive injuries followed by the use of either mild or moderate
hypothermia. Impact-acceleration injury was used to elicit mTBI and
vascular function was assessed through the use of cranial windows,
followed by postmortem analysis of amyloid precursor protein im-
munoreactivity to assess the burden of axonal damage.
In rats of 8 weeks in age, a significantly reduced impact severity
was needed to elicit cerebral vascular and axonal abnormalities
compared to that previously reported in adults. Moreover in the 7
week rats, even further reductions in injury severity resulted in
comparable changes. Further, in the juvenile rats, the window of risk
between repetitive insults was significantly elongated compared to
that seen in adults. Lastly, only the use of moderate hypothermia
proved neuroprotective in the juvenile rats.
In conclusion, juvenile rats are more vulnerable to lower thresholds
of injury for longer intervals between injuries compared to adult rats,
with the caveat that moderate hypothermia can attenuate the damaging
consequences of repetitive injury.
Supported by NIH Grant # NS077675
Key words
axonal injury, hypothermia, impact accelaration injury, juvenile rats,
repetitive traumatic brain injury
B4-27
ACUTE MRS AND DTI FINDINGS AFTER MODERATE/
SEVERE PEDIATRIC TBI
Holshouser, B.
1
, Ghosh, N.
2
, Rundquist, M.
2
, Pivonka-Jones, J.
2
, Tong,
K.
1
, Ashwal, S.
2
1
Loma Linda University, Department of Radiology, Loma Linda, USA
2
Loma Linda University, Department of Pediatrics, Loma Linda, USA
We present findings on a prospective study comparing acute MRS and
DTI findings in pediatric TBI patients to age-matched controls.
Pediatric patients, ages 4 to 18 years, were enrolled if they sus-
tained moderate/severe TBI requiring (GCS
<
13) OR (GCS
>
13 if
evidence of intracranial injury on initial computed tomography
scan). Patients underwent 3T MRI with DTI and MRS in the acute
period (6–17 days post TBI). TBI and control regional DTI metrics
(FA, ADC, AD, RD) and MRS ratios (NAA/Cr, NAA/Cho, Cho/Cr)
for the acute study were compared, according to severity of injury to
age matched controls and correlated with neurologic (PCPCS) and
neuropsychological outcomes at 12 months; general measures of
memory utilizing the Children’s Memory Scale (CMS: General
Memory score), attention utilizing the Test of Everyday Attention
for Children (TEA-CH: Teach G score), and the Wechsler Abbre-
viated Scale of Intelligence (WASI: Full Scale IQ).
We studied 58 children (43M); mean age 12.2
3.5 yrs (5.2–
17.9 yrs); initial GCS (Mild
=
23; Moderate
=
8; Severe
=
27) and 54
controls; mean age 12.1
3.3 yrs (5.5–17.4 yrs). Initial studies were
obtained at 11.5
3.4 days after injury. Follow-up studies were ob-
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