{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:17:35Z","timestamp":1792034255259,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004418","name":"Vrije Universiteit Brussel","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004418","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Besides seizures, patients with epilepsy are affected by a variety of cognitive and psychiatric comorbidities that further impair their quality of life. The present study provides an in\u2010depth characterization of the behavioral alterations induced by 6\u00a0Hz corneal kindling. Furthermore, we correlate these behavioral changes to alterations in c\u2010Fos protein expression throughout the brain following kindling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adolescent male Naval Medical Research Institute (<jats:styled-content style=\"fixed-case\">NMRI<\/jats:styled-content>) mice were kindled via repetitive subconvulsive 6\u00a0Hz corneal stimulations until they reached the fully kindled state (defined as 10 consecutive generalized seizures). Afterwards we performed an elaborate battery of behavioral tests and we evaluated c\u2010Fos expression throughout the brain using immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fully kindled mice display an abnormal behavioral phenotype, characterized by basal and amphetamine\u2010induced hyperlocomotion, anhedonia, social withdrawal, and deficits in short\u2010 and long\u2010term memory. Moreover, 6\u00a0Hz corneal kindling enhances c\u2010Fos immunoreactivity in the visual, parahippocampal, and motor cortices and the limbic system, whereas c\u2010Fos<jats:sup>+<\/jats:sup> cells are decreased in the orbital cortex of fully kindled mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The behavioral outcomes of 6\u00a0Hz corneal kindling cluster into 3 main categories: positive symptoms, negative symptoms, and cognitive impairment. These symptoms are accompanied by c\u2010Fos activation in relevant brain regions once the fully kindled state is established. Based on the face validity of this model, we speculate that 6\u00a0Hz corneal kindling can be used to model not only pharmacoresistant limbic seizures, but also several neurobehavioral comorbidities that affect patients with epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13943","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T05:56:38Z","timestamp":1511157398000},"page":"67-78","source":"Crossref","is-referenced-by-count":28,"title":["6\u00a0Hz corneal kindling in mice triggers neurobehavioral comorbidities accompanied by relevant changes in c\u2010Fos immunoreactivity throughout the brain"],"prefix":"10.1111","volume":"59","author":[{"given":"Giulia","family":"Albertini","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information Center for Neurosciences Vrije Universiteit Brussel Brussels 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