{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:48:28Z","timestamp":1791308908050,"version":"4.3.1"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,9,8]],"date-time":"2018-09-08T00:00:00Z","timestamp":1536364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["602102 (EPITARGET) \/16\u201005"],"award-info":[{"award-number":["602102 (EPITARGET) \/16\u201005"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Because brain inflammation may contribute to the pathophysiology of temporal lobe epilepsy (<jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>), we investigated the expression of various inflammatory markers of the innate and adaptive immune system in the epileptogenic human and rat hippocampus in relation to seizure activity and blood\u2010brain barrier (<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>) dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemistry was performed using various immune cell markers (for microglia, monocytes, macrophages, T lymphocytes, and dendritic cells) on hippocampal sections of drug\u2010resistant<jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>patients and patients who died after status epilepticus. The expression of these markers was also studied in the electrical post\u2013status epilepticus rat model for<jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>, during the acute, latent, and chronic epileptic phase.<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>dysfunction was assessed using albumin immunohistochemistry and the<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>tracer fluorescein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Monocyte infiltration, microglia, and perivascular macrophage activation were persistently increased in both epileptogenic human and rat hippocampus, whereas T lymphocytes and dendritic cells were not or were scarcely detected. In addition to this, increased expression of C\u2010C motif ligand 2 (<jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>2) and osteopontin was observed. In humans, the expression of<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>68 and<jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>2 was related to the duration of epilepsy and type of pathology. In rats, the expression of<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>68,<jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>2, and the perivascular macrophage marker<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>163 was related to the duration of the initial insult and to the number of spontaneous seizures. Interestingly, the number of<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>163\u2010positive perivascular macrophages was also positively correlated to<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>dysfunction in chronic epileptic rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These data suggest a proepileptogenic role for monocytes\/macrophages and other cells of the innate immune response, possibly via increased<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>leakage, and indicate that T cells and dendritic cells, which are closely associated with the adaptive immune response, are only sparsely infiltrated during epileptogenesis in the electrical post\u2013status epilepticus rat model. Future studies should reveal the relative importance of these immune cells and whether specific manipulation can modify or prevent epileptogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14550","type":"journal-article","created":{"date-parts":[[2018,9,8]],"date-time":"2018-09-08T11:30:27Z","timestamp":1536406227000},"page":"1931-1944","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Activation of the innate immune system is evident throughout epileptogenesis and is associated with blood\u2010brain barrier dysfunction and seizure progression"],"prefix":"10.1111","volume":"59","author":[{"given":"Diede W. 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