Inflammation independent epileptogenesis in vitro

This article is distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Alerts: Sign up at eneuro.org/alerts to receive customized email alerts when the fully formatted version of this article is published. What elements of the inflammatory system are necessary for epileptogenesis in vitro? This is a confidential document and must not be discussed with others, forwarded in any form, or posted on websites without the express written consent of eNeuro. Abstract 43 Epileptogenesis in vivo can be altered by manipulation of molecules such as cytokines and 44 complement that subserve intercellular signaling in both the inflammatory and central nervous 45 systems. Because of the dual roles of these signaling molecules, it has been difficult to precisely 46 define the role of systemic inflammation in epileptogenesis. Organotypic hippocampal brain 47 slices can be maintained in culture independently of the systemic inflammatory system, and the 48 rapid course of epileptogenesis in these cultures supports the idea that inflammation is not 49 necessary for epilepsy. However, this preparation still retains key cellular inflammatory 50 mediators. Here we found that rodent hippocampal organotypic slice cultures depleted of T 51 lymphocytes and microglia developed epileptic activity at essentially the same rate and to 52 similar degrees of severity as matched control slice cultures. These data support the idea that 53 although the inflammatory system, neurons, and glia share key intercellular signaling molecules, 54 neither systemic nor CNS-specific cellular elements of the immune and inflammatory systems 55 are necessary components of epileptogenesis. The inflammatory and central nervous systems share many signaling molecules, compromising 60 the utility of traditional pharmacological and knockout approaches in defining the role of 61 inflammation in CNS disorders such as epilepsy. In an in vitro model of post-traumatic 62 epileptogenesis, the development of epilepsy proceeded in the absence of the systemic 63 inflammatory system, and was unaffected by removal of cellular mediators of inflammation 64 including macrophages and T-lymphocytes. These results are not meant to disprove the idea 65 that " inflammation causes epilepsy " but rather circumscribe the overlap between the 66 4 inflammatory system vs. the CNS mechanisms that are operative during post-traumatic 67 epileptogenesis.