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Differential Regulation of Cytokine Expression Following Pilocarpine-Induced Seizure

Jankowsky, Joanna L. and Patterson, Paul H. (1999) Differential Regulation of Cytokine Expression Following Pilocarpine-Induced Seizure. Experimental Neurology, 159 (2). pp. 333-346. ISSN 0014-4886. doi:10.1006/exnr.1999.7137.

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While the pathological changes that occur in the brain following seizure have been well characterized, the molecular mechanisms underlying these events are poorly understood. Cell death, reactive gliosis, and axonal sprouting are among the best studied alterations in the epileptic brain. Previous work in both the peripheral and the central nervous systems suggests that cytokines are capable of affecting each of these processes. To better understand the role of cytokines in seizures and their sequelae, we have characterized cytokine expression in an animal model of epilepsy. Using pilocarpine to chemically induce seizures, and RNase protection assays to assess mRNA levels, we have quantified changes in expression of several members of the neuropoietic cytokine family following a single, prolonged seizure. Levels of oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1, and ciliary neurotrophic factor were all increased in the hippocampus after seizure, though to differing extents and with markedly different time courses. Cells expressing the most dramatically up-regulated cytokines, LIF and OSM, were identified by combined in situ hybridization and immunohistochemistry. The majority of LIF^+ cells in the hippocampus were glial fibrillary acidic protein^+ astrocytes, while the majority of OSM^+ cells had the morphology of interneurons and were occasionally colabeled with neurofilament markers. Both the time course and the localization of cytokine up-regulation following seizure suggest possible roles for these intercellular signaling molecules in epilepsy.

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Jankowsky, Joanna L.0000-0002-5593-2310
Additional Information:© 1999 by Academic Press. Received January 13, 1999; accepted May 8, 1999. We thank Joaquin Gutierrez, Robert Vega, Janet Baer, and Andy Groves for help with handling and care of the animals in this study. Their efforts were invaluable in the course of this work. We also thank Adam Mamelak, Lisa Banner, Andy Groves, Sherry Perez, Alice Paquette, Amy Greenwood, and Pat White for continued advice and technical guidance. Helpful comments on the manuscript were offered by Kai Zinn, Andy Groves, and Adam Mamelak. Laboratory support from Doreen McDowell and Bill Lease is gratefully acknowledged. This work was supported by NINDS Grant 20916 and NRSA Training Grant 5 T32 GM 07737. A preliminary report on some of these findings has appeared previously (24).
Funding AgencyGrant Number
NIH Predoctoral Fellowship5 T32 GM 07737
Subject Keywords:hippocampus; cytokine; epilepsy; seizure; pilocarpine; leukemia inhibitory factor; LIF; oncostatin M; OSM; ciliary neurotrophic factor; CNTF; cardiotrophin-1; CT-1; astrocyte.
Issue or Number:2
Record Number:CaltechAUTHORS:20160323-080524579
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Official Citation:Joanna L. Jankowsky, Paul H. Patterson, Differential Regulation of Cytokine Expression Following Pilocarpine-Induced Seizure, Experimental Neurology, Volume 159, Issue 2, October 1999, Pages 333-346, ISSN 0014-4886,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65605
Deposited By: Ruth Sustaita
Deposited On:23 Mar 2016 15:36
Last Modified:06 Jun 2023 19:42

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