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Brain Advance Access published online on November 7, 2003
Brain, doi:10.1093/brain/awh038
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© 2003 The Guarantors of Brain

Article

Post-traumatic epilepsy following fluid percussion injury in the rat

Raimondo D’Ambrosio 1*, Jared P. Fairbanks 2, Jason S. Fender 3, Donald E. Born 4, Dana L. Doyle 5, and John W. Miller 6

1 Department of Neurological Surgery, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA; Department of Neurology, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA; Regional Epilepsy Center, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA; Center on Human Development and Disability, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA
2 Department of Neurological Surgery, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA
3 Department of Neurological Surgery, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA
4 Department of Pathology, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA; Center on Human Development and Disability, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA
5 Department of Pathology, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA
6 Department of Neurological Surgery, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA; Department of Neurology, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA; Regional Epilepsy Center, University of Washington, School of Medicine, Harborview Medical Center, Seattle, WA 98104, USA

* Corresponding author. E-mail: raid{at}u.washington.edu.

Received 17 June 2003 ; revised 4 September 2003 ; accepted 5 September 2003

Abstract

The lack of an adequate model of post-traumatic epilepsy (PTE), in which, similarly to the human condition, chronic spontaneous focal seizures follow a single episode of traumatic brain injury, has hampered the identification of clinically relevant epileptogenic mechanisms and the development of effective therapies. We studied the electrophysiological, behavioural and structural consequences of a clinically relevant model of closed head injury, the lateral fluid percussion injury (FPI), in the rat. We found that a single episode of severe FPI is sufficient to cause PTE. Chronic electrocorticography (ECoG) demonstrated spontaneous chronic seizures that were partial, originated from the neocortex at the site of injury, and progressively worsened and spread over time. The cases of epilepsy in the post-traumatic population increased over time following injury. Post-FPI epileptic rats exhibited pauses in their behaviour, facial automatisms and myoclonus at the time of epileptiform ECoG events. In vitro local field potential recordings demonstrated persistent hyperexcitability of the neocortex at and around the site of injury that was associated with intense glial reactivity. These results for the first time demonstrate persistent hyperexcitability of the injured neocortex and define a useful model for pathophysiological studies of basic mechanisms of spontaneous epileptogenesis and for preclinical screening of effective antiepileptogenic drugs.

Keywords: traumatic brain injury; epileptogenesis; electrocorticography; drug screening; gliosis.
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