Traumatic brain injury (TBI) is the leading cause of acquired epilepsy in western societies, and accounts for ~4% of epilepsy in the general population. The mechanisms of human epileptogenesis after TBI remain unknown, and no treatment exists to prevent it or even modify its development. Thus, many head injury patients develop posttraumatic epilepsy (PTE) and require life-long treatment. Mounting evidence indicates a role for inflammation in acquired epileptogenesis. Inflammation is a consistent feature of both the injured brain and of the epileptic brain, and several inflammatory mediators also affect seizure susceptibility. The rational development of anti-inflammatory prophylaxes for PTE requires understanding of the diverse components of inflammation that are necessary for posttraumatic epileptogenesis. This has been hindered by the lack of an effective treatment that prevents posttraumatic epileptogenesis. Using an etiologically realistic model of PTE that induces progressive inflammation and epileptogenesis, we have recently identified a powerful antiepileptogenic effect of mild focal cooling (D'Ambrosio et al., Ann Neurol doi: 10.1002/ana.23764). The present proposal aims to use mild focal cooling as a tool to understand which aspects of the inflammatory processes in the perilesional neocortex that becomes the epileptic focus are necessary for epileptogenesis. We will use gene-array, RT-PCR, Luminex-based assays and immunohistochemistry to lay the ground work necessary to identify specific features of inflammation in the incipient epileptic focus that can be targeted fo prophylactic intervention.
Inflammation is a consistent feature of both the injured brain and of the epileptic brain, and mounting evidence indicates a role for inflammation in acquired epileptogenesis. The rational development of anti-inflammatory prophylaxes for PTE requires the understanding of the diverse components of inflammation that are necessary for posttraumatic epileptogenesis. Our proposed studies will use a realistic model of posttraumatic epileptogenesis, and an effective treatment that prevents it, to dissect out the inflammatory mediators involved in epileptogenesis after head injury.
|Kadam, Shilpa D; D'Ambrosio, Raimondo; Duveau, Venceslas et al. (2017) Methodological standards and interpretation of video-electroencephalography in adult control rodents. A TASK1-WG1 report of the AES/ILAE Translational Task Force of the ILAE. Epilepsia 58 Suppl 4:10-27|