{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:15:31Z","timestamp":1791396931265,"version":"4.3.3"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T00:00:00Z","timestamp":1504051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"ERANET-NEURON","award":["JTC2014 BriE ANR14 Neur0004"],"award-info":[{"award-number":["JTC2014 BriE ANR14 Neur0004"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["FP7 (DESIRE) No. 602531"],"award-info":[{"award-number":["FP7 (DESIRE) No. 602531"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Italian Ministry of Health","award":["RF-2011-02350578"],"award-info":[{"award-number":["RF-2011-02350578"]}]},{"name":"EPICARE"},{"name":"Paolo Zorzi Association for Neuroscience"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The contribution of recurring seizures to the progression of epileptogenesis is debated. Seizure\u2010induced brain damage is not conclusively demonstrated either in humans or in animal models of epilepsy. We evaluated the expression of brain injury biomarkers on postsurgical brain tissue obtained from 20 patients with frequent seizures and a long history of drug\u2010resistant focal epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression patterns of specific glial, neuronal, and inflammatory molecules were evaluated by immunohistochemistry in the core of type II focal cortical dysplasias (FCD\u2010II), at the FCD boundary (perilesion), and in the adjacent normal\u2010appearing area included in the epileptogenic region. We also analyzed surgical specimens from cryptogenic patients not presenting structural alterations at imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Astroglial and microglial activation, reduced neuronal density, perivascular CD3\u2010positive T\u2010lymphocyte clustering, and fibrinogen extravasation were demonstrated in the core of FCD\u2010II lesions. No pathological immunoreactivity was observed outside the FCD\u2010II or in cryptogenetic specimens, where the occurrence of interictal and ictal epileptiform activity was confirmed by either stereo\u2010electroencephalography or intraoperative electrocorticography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Recurrent seizures do not induce the expression of brain damage markers in nonlesional epileptogenic cortex studied in postsurgical tissue from cryptogenic and FCD patients. This evidence argues against the hypothesis that epileptiform activity per se contributes to focal brain injury, at least in the neocortical epilepsies considered here. Ann Neurol 2017;82:331\u2013341<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25005","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T15:28:04Z","timestamp":1501169284000},"page":"331-341","source":"Crossref","is-referenced-by-count":67,"title":["Seizure activity per se does not induce tissue damage markers in human neocortical focal epilepsy"],"prefix":"10.1002","volume":"82","author":[{"given":"Laura","family":"Rossini","sequence":"first","affiliation":[{"name":"Epilepsy Unit, C. Besta Neurological Institute Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Garbelli","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, C. 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