21 / 162
A2-06
THE PERFLUOROCARBON NVX-108 INCREASED BRAIN
TISSUE OXYGENATION AFTER CONTROLLED CORTICAL
IMPACT BRAIN INJURY IN THE RAT
Saad Mullah
1
, Biswajit Saha
1
, Rania Abutarboush
1
, Ashraful Haque
1
,
Francoise Arnaud
1,2
, Brittany Hazzard
1
, Charles Auker
1
, Richard
McCarron
1,2
, Paula Moon-Massat
1
, Anke Scultetus
1,2
1
Naval Medical Research Center, Neurotrauma, OUMD, Silver
Spring, USA
2
Uniformed Services University of the Health Sciences, Department of
Surgery, Bethesda, USA
Hypoxia is a critical secondary injury mechanism in traumatic brain
injury (TBI), and early intervention to alleviate post-TBI hypoxia
may be beneficial. NVX-108 (NuvOx Pharma, Tucson, AZ), a do-
decafluoropentane perfluorocarbon, was screened for its effect on
brain tissue oxygenation (PbtO
2
) when administered soon after TBI.
Anesthetized rats ventilated with 40% oxygen underwent moderate
controlled cortical impact (CCI) TBI at time 0 (T0). Rats received
either no treatment (NON, n
=
8) or 0.5 ml/kg intravenous (IV) NVX-
108 (NVX, n
=
9) at T15 (15 min after TBI) and T75. Brain tissue
oxygenation was measured non-invasively using phosphorescence
quenching method (PQM). After CCI-TBI, PbtO
2
dropped by
48
–
6% (p
<
0.001) in the NVX group and by 46
–
5% (p
<
0.001) in
the NON group compared to baseline. Throughout the rest of the
study period (155 min) PbtO
2
in the NON group never recovered and
remained at the immediate post-injury level (16
–
2 mm Hg). In NVX
group, NVX-108 infusion resulted in a steady increase in PbtO
2
, and
at T115 it recovered to pre-injury values. At T135, PbtO
2
was sig-
nificantly higher (p
<
0.05) compared to post-injury values. This
increase in PbtO2 was maintained until the end of the study. No
changes were noted in hemodynamics, body temperature, acid-base
balance, electrolytes or hemoglobin concentration. In conclusion, the
perfluorocarbon NVX-108 caused an increase in PbtO
2
following
moderately severe CCI-TBI in rats and should be evaluated further
as a possible immediate treatment for TBI.
Keywords: PbtO2, oxygen therapeutics, phosphorescence, PFC
A2-07
OXYGEN CARRIER M-101 DID NOT CAUSE VASOCON-
STRICTION AND IMPROVED CEREBRAL OXYGENATION
AFTER TBI IN RATS
Rania Abutarboush
1
, Saad Mullah
1
, Biswajit Saha
1
, Ashraful
Haque
1
,
Francoise Arnaud
1,2
,
Charles Auker
1,2
,
Richard
McCarron
1,2
, Paula Moon-Massat
1
, Anke Scultetus
1,2
1
Naval Medical Research Center/ Henry Jackson Foundation, Neu-
rotrauma, Silver Spring, USA
2
Uniformed Services Universityof the Health Sciences, Department of
Surgery, Bethesda, USA
The severity of traumatic brain injury (TBI) may be reduced if ox-
ygen can be rapidly provided to the injured brain. This study eval-
uated if the oxygen-carrier M-101 (Hemarina, France) causes
vasoconstricton of pial vasculature in healthy rats (experiment 1) and
if it improves brain tissue oxygen (PbtO
2
) in rats after controlled-
cortical impact (CCI)-TBI (experiment 2). Experiment 1: M-101 was
infused at 12.5 ml/kg IV over 2 h into anesthetized, healthy rats.
Intravital microscopy was used to assess pial artery diameter over
time. There was a mild (9 mm Hg) increase in the mean arterial
blood pressure (MAP) without constriction of pial arterioles. Ex-
periment 2: Anesthetized rats underwent CCI-TBI. 15 min after in-
jury M-101 was infused IV (12 ml/kg over 1 h). Brain tissue
oxygenation was assessed non-invasively via phosphorescence
quenching method (PQM). In both M-101 and untreated control
(NON) groups, PbtO
2
was
*
30
–
2 mm Hg pre-injury and decreased
(P
£
0.05) to
*
16
–
2 mm Hg 15 min after CCI. In the NON group,
PbtO
2
remained
*
50% of baseline until the end of the study. M-101
administration resulted in a sustained increase in PbtO
2
(peak:
25
–
5 mm Hg), which elevated PbtO
2
to pre-injury values. At the
end of the 155 min observation period, PbtO
2
slowly decreased be-
low pre-injury levels, but was still higher than the NON group.
Histopathology showed no differences between groups, possibly due
to the short study duration. In conclusion, M-101 increased systemic
blood pressures without concurrent cerebral pial vasoconstriction (in
healthy rats) and restored PbtO
2
to 86% of pre-injury for at least
80 min when given soon after CCI-TBI. M-101 should be evaluated
in a clinically relevant large animal model for pre-hospital treatment
of TBI.
Keywords: hemoglobin-based oxygen carrier, oxygen therapeu-
tic, pial microcirculation, brain oxygenation, controlled cortical
impact
A2-08
TREATMENT AND RISK FACTORS FOR POST-TRAUMATIC
EXTERNAL HYDROCEPHALUS FOLLOWING DECOM-
PRESSIVE CRANIECTOMY
Wei Yan
1
, Shi-Di Yang
2
, Qun Wu
1
, Gao Chen
1
, Jian-Min Zhang
1
1
The Second Affiliated Hospital, Zhejiang University, Neurosurgery,
Hangzhou, China
2
Ningbo Medical Treatment Center Lihuili Hospital, Neurosurgery,
Ningbo, China
Objectives:
Both external hydrocyphalus and simple subdural hy-
groma following decomprassive craniectomy (DC) have been ob-
served in a variety of traumatic brain injury (TBI) patients. In the
early stage of most external hydrocyphalus cases, subdural fluid col-
lection is the only significant signs on CT scans. Therefore, it is
difficult to different early-stage external hydrocyphalus from simple
subdural hygroma, resulting in inappropriate treatment and poor
prognosis. In this study we assessed the risk factors for the develop-
ment of external hydrocyphalus after DC, and the treatment strategies
were also discussed.
Methods:
A retrospective analysis was undertaken of TBI patients
treated with DC at The Second Affiliated Hospital, Zhejiang Uni-
versity between January 2012 and December 2013. Risk factors for
hydrocephalus were evaluated by using logistic regression analysis.
Results:
Sixty-one patients with subdural fluid collection after DC
were included in this study. Twenty cases developed clinical evidence
of hydrocyphalus and required a ventriculoperitoneal shunt (VPS).
Intraventricular hematoma (p
=
0.009), interhemispheric hygroma
(p
=
0.003) and the onset time of sudural fluid collection (p
=
0.006)
were independent risk factors for external hydrocyphalus after DC.
VPS and early cranioplasty were effective for external hydrocephalus
patients.
Conclusions:
Our results suggested that intraventricular hematoma,
interhemishperic hygroma and onset time of subdural fluid collection
could be predictors for external hydrocephalus after DC. Early cra-
nioplasty and VPS not subdural peritoneal shunt should be considered
for this clinical entity.
Keywords: Traumatic Brain Injury, Hydrocephalus, Subdural Hy-
groma, Decompressive Craniectomy
A-21