[Abstract Title]. - Society for Neuroscience

Abstract: Temporal lobe epilepsy is a common consequence of traumatic brain injury, but
fundamental aspects of epileptogenesis after trauma remain poorly understood. Identifying
experimental models that exhibit similar pathology to injury-induced epilepsy in humans is
necessary to elucidate underlying mechanisms by which the injured brain becomes epileptic.
Using the controlled cortical impact (CCI) injury model, we examined whether mice developed
spontaneous seizures after moderate (0.5mm injury depth) or severe (1.0mm injury depth) brain
injury and how subsequent posttraumatic mossy fiber sprouting was associated with excitability
in the dentate gyrus 42-71d post-injury. Days to weeks after injury, spontaneous seizures were
observed in 36% of mice with severe and 20% of mice after moderate injury. Timm staining
revealed mossy fiber sprouting in the inner molecular layer of the dentate gyrus in 55% of mice
after severe injury and 20% of mice after moderate injury. Sprouting was typically localized in
septal areas of the dentate gyrus ipsilateral to the injury. Extracellular field-potential recordings
were made in isolated hippocampal brain slices to examine excitability after injury. Stimulation
of perforant path revealed a significant reduction (P < 0.01) in paired-pulse responses in dentate
granule cells at 20ms (47%) and 40ms (59%) interpulse intervals in slices from injured animals
with mossy fiber sprouting compared to controls; no difference was detected at 80ms or 160ms
intervals. Responses in slices from injured animals that did not display mossy fiber sprouting
were not different from controls at any interval. In the presence of Mg 2+ - free ACSF containing
100µM picrotoxin, slices with mossy fiber sprouting were characterized by spontaneous and
hilar-evoked epileptiform activity in the dentate gyrus. These data suggest the development of
spontaneous posttraumatic seizures as well as structural and functional network changes
associated with temporal lobe epilepsy in the mouse dentate gyrus by 71d after CCI injury.
Disclosures: R.F. Hunt , University of Kentucky, A. Employment (full or part-time); Epilepsy
Foundation, B. Research Grant (principal investigator, collaborator or consultant and pending
grants as well as grants already received); S.W. Scheff, University of Kentucky, A. Employment
(full or part-time); NIH AG21981, B. Research Grant (principal investigator, collaborator or
consultant and pending grants as well as grants already received); B.N. Smith, University of
Kentucky, A. Employment (full or part-time); NS 052302, B. Research Grant (principal
investigator, collaborator or consultant and pending grants as well as grants already received).
Poster
250. Epilepsy: Networks
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 250.2/V14
Topic: C.06.f. Circuits and systems
Support: Dr. Ralph and Marian Falk Medical Research Trust