Page 72 - NNS 2014 Program & Abstract Book

A4-10
GFAP AUTOANTIBODY DEVELOPMENTAL TRAJECTORIES
AFTER TBI: CHARACTERIZATION AND ASSOCIATIONS
WITH INFLAMMATORY MARKERS
Ritter, A.C.1, Zhang, Z.4,5, Wang, K.K.4,5, Wagner, A.K.1–3
1Department of PM&R, Pittsburgh, United States
2Safar Center for Resuscitation Research, Pittsburgh, United States
3Center for Neuroscience, University of Pittsburgh, Pittsburgh, Uni-
ted States
4Center for Neuroproteomics & Biomarker Research, Gainesville,
United States
5Department of Psychiatry, University of Florida, Gainesville, United
States
Following blood brain barrier disruption after traumatic brain injury
(TBI), brain proteins enter the peripheral circulatory system where
they may trigger an immune response. Glial fibrillary acidic protein
(GFAP) is expressed within the central nervous system, and levels are
elevated following TBI. Recently, our work identified the presence of
autoantibodies (AutoAb) toward GFAP following TBI. Also, IL-7 is
important for immune cell development and is implicated in auto-
immune neurodegenerative diseases like multiple sclerosis. Thus, we
explored 1) temporal GFAP autoAb development after severe TBI, 2)
relationships between GFAP AutoAb longitudinal profiles and early
cerebrospinal fluid (CSF) GFAP levels, and 3) concurrent IL-7 asso-
ciations with GFAP autoAb production among TBI survivors. Acute
CSF and serum, along with chronic serum samples (up to 6 months
post-injury) were obtained from 36 adults with TBI; CSF and serum
samples were obtained from 20 controls. Samples were assayed to
measure CSF GFAP and GFAP autoAb, and serum GFAP autoAb and
IL-7 levels. Absolute autoAb level and fold-change from acute
baseline GFAP autoAb were compared between TBI cases and con-
trols and to IL-7 levels. We used group-based trajectory analysis to
identify two distinct temporal GFAP autoAb profiles showing sig-
nificantly different GFAP AutoAb levels across the sampling period.
GFAP AutoAb was higher in cases versus controls at all chronic time-
points (p < 0.005). Acute GFAP AutoAb correlated with chronic
GFAP AutoAb levels (p < 0.05), and serum GFAP autoAb correlated
with serum IL-7 at multiple chronic time-points. Additionally, IL-7
levels differed between trajectory groups at multiple time-points
(p < 0.05). This is the first study to describe temporal GFAP autoAb
profiles following TBI and to implicate inflammation, particularly
IL-7, as a possible contributor to autoimmune response development
post-TBI.
CDCR49 CCR323155; DODW81XWH-071-0701
Key words
auto-antibody, cytokine, GFAP, traumatic brain injury
A4-11
METABOLOMIC ANALYSIS OF BIOFLUIDS FROM PA-
TIENTS WITH SEVERE TRAUMATIC BRAIN INJURY: IN-
FLUENCE OF CEREBRAL LACTATE SUPPLEMENTATION
Glenn, T.C.1, MacFarlane, M.P.1, Horning, M.2, Brooks, G.A.2 , Vespa,
P.A.1, Hovda, D.A.1, Martin, N.A.1
1University of California, Los Angeles, Los Angeles, USA
2University of California, Berkeley, Berkeley, USA
We have previously shown that the human brain can utilize lactate
as a fuel after severe traumatic brain injury (TBI). We hypothesize
that a detailed metabolomic analysis of patient body fluids during
lactate infusion would reveal important improvements in cerebral
metabolism.
Cerebral spinal fluid (CSF), arterial and jugular blood were col-
lected from 6 severely injured TBI patients (5 male, 1 female; age
26.5 – 14.0, admission GCS 6.8 – 3.4) at baseline and 3 hours after the
start of sodium l-lactate infusion (90 mg/min). Samples were centri-
fuged and frozen at - 80o C and shipped to Metabolon (Research
Triangle, NC). Biofluid analysis included GC/MS and UPLC-MS/MS.
Statistical analysis included significance tests and classification
analysis. For pair-wise comparisons, Welch’s t-tests and/or Wilcox-
on’s rank sum tests were used on the R platform.
Analysis of CSF and arterial and jugular plasma identified 197 and
335 biochemicals, respectively. Statistical analysis of CSF showed
statistical significance (p < 0.05) and trends (p < 0.1) in 5 and 9 me-
tabolites, respectively. Plasma samples showed statistical significance
and trends in 22 and 19 metabolites, respectively. CSF pathway anal-
ysis detected trends towards reduced glycolysis and pentose phosphate
metabolite levels as a result of lactate infusion. Additionally trends of
1-1.2 fold increases in TCA cycle metabolites were also seen. TCA
cycle differences were also observed in arterial and jugular plasma.
Interestingly, fructose levels were increased in arterial and decreased in
jugular plasma indicating a cerebral uptake of this sugar molecule.
These data support the notion that lactate nutritional supplemen-
tation can significantly affect cerebral metabolism. Positive effects on
TCA metabolism indicate that lactate can be beneficial to the injured
brain. Although small in size, this study demonstrates the utility of
metabolomic analysis of biofluids from TBI patients.
Acknowledgments
This research was supported by the UCLA Brain Injury Research
Center, and NINDS 1P01NS058489-01.
Key words
cerebral metabolism, metabolomics, recovery of function
A4-12
C-REACTIVE PROTEIN AUGMENTS THE DIAGNOSTIC
VALUE OF GLIAL FIBRILLARY ACIDIC PROTEIN IN DE-
TECTING ACUTE CT INTRACRANIAL PATHOLOGY
Yue, J.K.1 , Cooper, S.R.1, Diaz-Arrastia, R.2 , Wang, K.K.3, Sorani,
M.D.1, Lingsma, H.F.4, Yuh, E.L.1, Mukherjee, P.1, Valadka, A.B.5,
Gordon, W.A.6, Okonkwo, D.O.7, Manley, G.T.1
1Brain and Spinal Injury Center, University of California, San
Francisco, CA, USA
2Center for Neuroscience and Regenerative Medicine, Bethesda, MD,
USA
3Center for Neuroproteomics and Biomarkers Research, Gainesville,
FL, USA
4Erasmus Medical Center, Rotterdam, The Netherlands
5Seton Brain and Spine Institute, Austin, TX, USA
6Mount Sinai School of Medicine, New York, NY, USA
7University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Glial fibrillary acidic protein (GFAP) is released following paren-
chymal brain injury and has been studied as a potential diagnostic
biomarker. The liver-derived C-reactive protein (CRP) is a stable
plasma marker and its production increases following acute trauma.
We examined concurrent plasma GFAP and CRP in a cohort of 61
patients enrolled in the multicenter observational Transforming Re-
search and Clinical Knowledge in TBI (TRACK-TBI) Pilot Study.
Blood samples were collected < 24 hours of acute TBI and analyzed.
In addition to GFAP, CRP was identified as a potential useful TBI
biomarker. In patients with intracranial lesions on brain CT ( + CT),
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