title: Characterization of monocyte chemoattractant protein-1 expression following a kainate model of status epilepticus.
abstract: Brain injury due to seizure induces a robust inflammatory response that involves multiple factors. Although the expression of chemokines has been identified as a part of this response, there are remaining questions about their relative contribution to seizure pathogenesis. To address this, we report the expression profile of the chemokine, monocyte chemoattractant protein-1 (MCP-1, CCL2), during kainate-induced seizure in the rat hippocampus. Furthermore, we compare MCP-1 expression to the temporal profile of blood-brain barrier (BBB) permeability and immune cell recruitment at the injury site, since both of these events have been linked to MCP-1. We find that BBB permeability increased prior to upregulation of MCP-1, while MCP-1 upregulation and immune cell recruitment occurred concurrently, 7-13 h after opening of the BBB. Our findings support the following conclusions: (1) BBB opening to large proteins does not require MCP-1 upregulation; (2) Leukocyte immigration is not sufficient to induce BBB opening to large proteins; (3) MCP-1 upregulation likely mediates recruitment of macrophages/microglia and granulocytes during seizure injury, thus warranting further investigation of this chemokine.
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, CA, USA. nmanley@stanford.edu
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Manley
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Bertrand
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Kinney
authors.forename: Tressia C
authors.initials: TC
authors.lastname: Hing
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sapolsky
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005070:Evans Blue; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; D018932:Chemokine CCL2; D005070:Evans Blue; D007608:Kainic Acid