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showed a pronounced seizure response to the convulsant pentylenetet-
razol (PTZ) compared to sham-operated controls, coincidental with
significant loss of hippocampal interneurons and pronounced astro-
gliosis. A heightened seizure response to PTZ was still apparent several
months later at adulthood, and associated with the presence of abnormal
mossy fiber sprouting in the ipsilateral hippocampus, a pathological
hallmark of epileptogenesis. In addition to pleiotropic roles in neurode-
generation, several inflammatory mediators including interleukin (IL)-1
b
have been implicated in the initiation and propagation of seizures. On-
going studies aim to elucidate the importance of such factors in persistent
hyperexcitability in the immature brain after traumatic injury.
Keywords: interleukin-1, cytokine, immature brain, epileptogenesis
S15-03
NON-CONVULSIVE SEIZURES OBSERVED 1 YEAR FOL-
LOWING TRAUMATIC BRAIN INJURY
Thomas Sick
, Justin Sick, Amade Bregy, Joseph Wasserman, Dalton
Dietrich, Helen Bramlett
University of Miami, Neurology, Miami, USA
Epilepsy is an important secondary consequence of traumatic brain injury
(TBI), recognized in TBI patients and reproduced reliably in animal
models of TBI. Early studies focused on convulsive seizures but non-
convulsive seizures also occur after TBI that are not easily detected by
behavioral analysis. In this study we examined electrocorticographic
(ECoG) seizures in freely behaving rats 1 year after fluid percussion brain
injury. Epidural electrodes were implanted over the ipsilateral cortex
anterior and posterior to the contusion site of rats that were naı¨ve or
received sham, mild, moderate or severe TBI. 24 hrs later ECoG activity
and video analysis was conducted in freely moving animals for 60min.
No animals showed convulsive seizures during the 60min recording
period. However, spontaneous spike and wave episodes were detected,
which were more prevalent in animals that had undergone TBI 1 year
earlier than in either naı¨ve or sham-operated animals. The spike and wave
episodes were quantified using custom seizure detection software that
incorporated fast Fourier transform and normalized multi-frequency
power spectral analysis. The non-convulsive seizures were accompanied
by behavioral immobility or ‘‘freezing’’, which was quantified using
Ethovision movement analysis software. The non-convulsive electro-
graphic seizures and freezing behavior appeared similar to seizures de-
scribed by other investigators as ‘‘absence-like seizures’’ in rodents. Our
data suggest that post-traumatic epilepsy may present 1 year after TBI in
rodents and may take the form of non-convulsive or sub-clinical seizures.
Keywords: chronic seizures, sub-convulsive seizures
WLW1 WINTR Lunch Workshop
WLW1-01
EXPERIENCE IN EXAMINATION OF HUMAN TBI TISSUE:
A NEGLECTED ART
William Stewart
Laboratory Medicine Building, Dept. of Neuropathology, Glasgow,
South Lanarkshire, United Kingdom
Repro-ducing neuro-patho-logical features of traumatic brain injury
(TBI) and its outcomes, including chronic traumatic encephalo-pathy
(CTE), in animal models is a major focus of neuro-trauma research.
How-ever, very few researchers have experience assessing human
tissue, as neuro-patho-logical examination of human TBI brains is not
a standard part of graduate training, and access to human brain tissue
is limited. In ad-di-tion, post-graduate trained neuro-patho-logists
with research in-ter-est or experience in TBI are few and far be-tween.
As a consequence, there is a danger that appre-ciation of the range and
ex-tent of patho-logies encountered in human TBI and the so called
‘normal’ variation in human neuro-patho-logy, for example arising
through age and influence of comorbid patho-logy, is lost. Further,
through lack of exposure to the variation and vagaries of working with
human tissue, awareness of common artefacts and pitfalls in in-ter-
pre-tation of histo-logical material can be diluted. In short, neuro-
patho-logy in-ter-pre-tation of human TBI tissue is challenging and
fraught with com-plexity and frustration, but if pro-gress is to be
made, it is unavoidable. Whilst tempting to focus on surrogates of
patho-logy in research, such as bio-marker or imaging studies, without
the neuro-patho-logy to validate these observations, their in-ter-pre-
tation can remain challenging and questionable. And while animal
models have undoubted attraction, unless these model some aspect of
human patho-logy, their value is debtable. From early neuro-patho-
logical studies carefully describing and documenting diffuse axonal
injury to more recent studies detailing neuro-degene-ration after TBI,
the con-tri-bution of careful neuro-patho-logical examination on
suitably pre-pared human brain tissue to our under-standing of the
consequences of traumatic brain injury can be traced through the
major milestones in TBI research and should remain in-tegral to re-
search studies in the future. During this WINTR Workshop the
challenges and benefits in working with human tissue will be re-
viewed, strategies to pro-ject design using human TBI material will be
outlined and the history and holdings of the unique Glasgow TBI
Archive will be dis-cussed.
Keywords: neuropathology, human studies, TBI, CTE
WLW1-02
BI-DIRECTIONAL TRANSLATIONAL STUDIES IN TBI: EX-
PERIMENTAL DESIGN USING HUMAN SAMPLES
Victoria Johnson
University of Pennsylvania, Neurosurgery, Philadelphia, USA
Traumatic brain injury (TBI) is a major health issue, exacting a consid-
erable health and economic burden on society. Furthermore, TBI is in-
creasingly recognized as a major risk factor for the development of
neurodegenerative disorders. However, despite decades of research, no
effective therapeutic agent has been successfully introduced to clinical
practice, with multiple failed phase 3 trials. While the reasons for these
failures are complex, the inability to translate therapeutic efficacy in
animal models to clinical efficacy in humans has been a major and re-
curring issue and raises questions over the relevance of preclinical data.
Paramount to any model is that it recapitulates pathologies arising in
human TBI. Further, any novel observations in TBI generated from
studies in animal models must be challenged in human tissue to confirm
relevance. This bi-directional translational principle in research is central
to ensuring applicability of animal models and in challenging novel ob-
servations in human tissue. As such, awareness of human neuropathology
studies in TBI, in particular the strengths and limitations of this work,
should be a fundamental objective for the field. Decades of careful studies
examining tissue from patients following TBI reveal a heterogeneous and
complex array of pathologies influenced by injury severity, comorbidities,
survival time, history of previous TBI and patient age, among many other
factors. As such, studies in human tissue carry complexities and chal-
lenges which must be borne in mind for study design. In particular, there
is a requirement in any study for inclusion of appropriately matched
controls to provide a baseline of ‘normal’ pathology against which pa-
thology in TBI material can be compared. Similarly, there is a need to
recognize inherent limitations in any archive of human bio-samples, such
as case selection bias. Nonetheless, appropriately designed studies in
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