Page 69 - NNS 2014 Program & Abstract Book

one male rats were randomly assigned to either moderate parasagittal
fluid percussion or sham injury. Blood serum samples were collected
2 days prior to TBI (baseline) and at 3, 6, and 24 hours after TBI.
Single CSF samples were collected from the cisterna magna 24 hours
after TBI, followed by euthanasia and brain harvesting for histology.
Serum and CSF samples were analyzed for fragmented GFAP and
UCH-L1 protein biomarkers using ELISA. Brain histology included
Fluoro-jade, hematoxylin and eosin stainings, and GFAP immuno-
staining. Serum and CSF levels of GFAP were near zero in sham
animals. Serum GFAP was significantly elevated to 5.81 – 1.31 ng/ml
(P < 0.001, n = 11) and 3.16 – 0.44 ng/ml (P < 0.05, n = 11) at 3 and 6
hours post TBI, respectively compared to baseline (0.01 – 0.01 ng/ml,
n = 10). CSF GFAP at 24 hours post TBI was significantly elevated
to 16.14 – 5.08 ng/ml (P < 0.01, n = 10) compared to sham (0.03 –
0.03 ng/ml, n = 10). Serum UCH-L1 was significantly elevated at 3
hours post TBI (0.83 – 0.08 ng/ml, P < 0.001, n = 11). CSF UCH-L1 at
24 hours post TBI was significantly elevated (26.83 – 6.31 ng/ml,
P < 0.01, n = 10) compared to sham (6.36 – 1.35 ng/ml, P < 0.01,
n = 10). Histology revealed characteristic acute neuronal degeneration
in the ipsilateral hippocampus and parietal cortex as well as hemor-
rhage along the corpus callosum and in the parietal cortex. These
results suggest that structural damage occurs in astrocytes acutely
following TBI. In this model of parasagittal focal contusion, bio-
markers of fragmented GFAP appear to be more robustly detected
than UCH-L1as an acute marker of brain damage after TBI.
Key words
fluid percussion, pathology, TBI
A4-02
DELAYED CONSCIOUSNESS, SENSORY-MOTOR DEFICITS,
AND GFAP LEVELS IN REPEATED CONCUSSIVE IMPACT
Boutte, A.M., Mountney, A., Johnson, D.W., Yarnell, A., Tortella,
F.C., Dave, J.R., Shear, D.A., Schmid, K.E.
Walter Reed Army Institute of Research, Silver Spring, USA
Developing diagnostic and prognostic biomarkers for mild traumatic
brain injury (mTBI) has become an urgent medical need. The purpose
of this study was to evaluate the effects of single and repeated mTBI
on regaining consciousness, sensory-motor deficits, and GFAP
abundance in biofluids. The projectile concussive impact (PCI) model
was used to induce mTBI. Anesthetized rats received zero (sham), one
(1xPCI) or repeated (2,3 or 4xPCI) impacts separated by 1 h intervals.
Righting reflex (RR) and sensory-motor deficits (revised neurobeha-
vioral severity scale, NSS-R) were recorded immediately following
the last impact. Serum and CSF GFAP were analyzed by ELISA 1 h
after the last concussion. Results showed significant PCI-induced al-
terations in RR and NSS-R scores following a single PCI (p < 0.05 vs.
Sham) both of which also showed significant (1.6–1.7 fold) increases
in magnitude following the 2nd PCI (p < 0.05 vs. 1xPCI). Although
both RR and NSS-R remained significantly elevated following a 3rd or
4th PCI (p < 0.05 vs. 1xPCI or Sham), no additional ‘‘stepwise’’ in-
creases were detected relative to the 2nd impact (p < 0.05 vs. 2xPCI).
Levels of GFAP in CSF increased to 1.9 ng/mL after a single PCI
(p < 0.05 vs. sham) and were further increased following repeated
concussions with mean levels of 3.9 ng/mL (2xPCI), 2.7 ng/mL (3xPCI)
and 7.5 ng/mL (4xPCI) (p < 0.05 vs. Sham). Notably, a significant
correlation was detected between RR scores and CSF GFAP following
4xPCI (p < 0.05). Consistent with this observation, serum GFAP levels
analyzed in the 4xPCI group was significantly increased vs. sham
(4xPCI= 0.06 ng/mL; Sham = 0.02 ng/mL; p <0.05). Overall, these results
suggest that single and repeated PCI lead to neurological impairments that
are associated with increased abundance of GFAP in CSF and serum.
Funded by CDMRP/DHP Grant W81XWH-12-2-0134.
Key words
concussion, GFAP, mild TBI, serum
A4-03
PLASMA ANTI-GFAP AUTOANTIBODY LEVELS DURING
ACUTE AND CHRONIC PHASES OF TBI - A TRACK-TBI
PILOT STUDY
Wang, K.K.1, Yang, Z.1, Zhang, Z.1, Yue, J.K.2, Puccio, A.M.3, Diaz-
Arrastia, R.4, Lingsma, H.F.5, Yuh, E.L.2,6, Mukherjee, P.2,6, Valadka,
A.B.7, Gordon, W.A.8 , Okonkwo, D.O.3, Manley, G.T.2, Cooper, S.R.2,6,
Dams-O’Connor, K.9 , Hricik, A.J.4, Inoue, T.2 , Maas, A.I.10, Menon,
D.K.11, Schnyer, D.M.12, Sinha, T.K.7
1Departments of Psychiatry, University of Florida, Gainesville, USA
2Department of Neurological Surgery, University of California, San
Francisco, USA
3Department of Neurological Surgery, University of Pittsburgh
Medical Center, Pittsburgh, USA
4Department of Neurology, Uniformed Services University of the
Health Sciences, and Center for Neuroscience, Bethesda, USA
5Department of Public Health, Erasmus Medical Center, Rotterdam,
The Netherlands
6Department of Radiology, University of California, San Francisco,
USA
7Seton Brain and Spine Institute, Austin, USA
8Department of Rehabilitation Medicine, Mount Sinai School of
Medicine, New York, NY, USA
9Department of Neurosurgery, Antwerp University Hospital, Edegem,
Belgium
10Division of Anaesthesia, University of Cambridge and Adden-
brooke’s Hospital, Cambridge, United Kingdom
11Department of Psychology, University of Texas, Austin, TX, USA
We recently described subacute serum anti-GFAP autoantibody after
severe traumatic brain injury (TBI). Here, we expanded our autoantibody
study to the multicenter observational study [TRACK-TBI Pilot] cohorts
that cover the full spectrum of TBI (GCS 3-15) including acute ( < 24 h)
plasma samples from 196 TBI patients, and a second cohort of 21 chronic
TBI subjects (average 188 days post-injury). We identified that those
subjects with self-reported prior TBI and loss of consciousness(LOC) had
higher day 1 anti-GFAP autoAb (mean 9.11 arbitrary unit, n = 43) when
compared to normal controls (mean 2.89; n = 16; p < 0.012). This data
suggest that exposure to TBI could trigger long-lived anti-GFAP auto-
antibody responses. Importantly, anti-GFAP autoAb levels in plasma
collected during the rehabilitation stage after TBI are significantly higher
(mean 15.08; n = 21) than normal controls, suggesting persisted up-
regulation of autoimmune response to brain antigen(s) following TBI.
Key words
autoantibody, biomarker, diagnosis, inflammation, outcome
A4-04
BRAIN INJURY SCREENING BY OCULAR ANALYSIS
(BISON)
Biswas, A.2, Menon, N.2, Bolton, A.N.1, Saatman, K.E.1, Geddes, J.W.1
1SCoBIRC, University of Kentucky, Lexington, USA
2Chromologic LLC, Pasadena, USA
A-37