Posttraumatic epilepsy after controlled cortical impact injury in mice

Robert F. Hunt, Stephen W. Scheff, Bret N. Smith

Research output: Contribution to journalArticlepeer-review

166 Scopus citations

Abstract

Many patients develop temporal lobe epilepsy after trauma, but basic mechanisms underlying the development of chronic seizures after head injury remain poorly understood. Using the controlled cortical impact injury model we examined whether mice developed spontaneous seizures after mild (0.5 mm injury depth) or severe (1.0 mm injury depth) brain injury and how subsequent posttraumatic mossy fiber sprouting was associated with excitability in the dentate gyrus 42-71 d after injury. After several weeks, spontaneous behavioral seizures were observed in 20% of mice with mild and 36% of mice with severe injury. Mossy fiber sprouting was typically present in septal slices of the dentate gyrus ipsilateral to the injury, but not in control mice. In slices with mossy fiber sprouting, perforant path stimulation revealed a significant reduction (P < 0.01) in paired-pulse ratios in dentate granule cells at 20 ms and 40 ms interpulse intervals, but not at 80 ms or 160 ms intervals. These slices were also characterized by spontaneous and hilar-evoked epileptiform activity in the dentate gyrus in the presence of Mg2+-free ACSF containing 100 μM picrotoxin. In contrast, paired-pulse and hilar-evoked responses in slices from injured animals that did not display mossy fiber sprouting were not different from controls. 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 71 d after CCI injury. Identifying experimental injury models that exhibit similar pathology to injury-induced epilepsy in humans should help to elucidate the mechanisms by which the injured brain becomes epileptic.

Original languageEnglish
Pages (from-to)243-252
Number of pages10
JournalExperimental Neurology
Volume215
Issue number2
DOIs
StatePublished - Feb 2009

Bibliographical note

Funding Information:
This research was supported by NIH NS052302 to B.N.S., NIH AG21981 to S.W.S., and an Epilepsy Foundation Training Fellowship to R.F.H. We wish to thank Kelly Roberts for technical assistance with the injury models.

Keywords

  • Dentate gyrus
  • Hyperexcitability
  • Mossy fiber sprouting
  • Seizures
  • Temporal lobe epilepsy
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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