{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T04:36:27Z","timestamp":1771043787192,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,4]],"date-time":"2014-04-04T00:00:00Z","timestamp":1396569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Thimet oligopeptidase (<jats:styled-content style=\"fixed-case\">TOP<\/jats:styled-content>) is a metalloprotease that has been associated with peptide processing in several nervous system structures, and its substrates include several peptides such as bradykinin, amyloid beta (A\u03b2), and major histocompatibility complex (<jats:styled-content style=\"fixed-case\">MHC)<\/jats:styled-content> class I molecules. As shown previously by our research group, patients with temporal lobe epilepsy (TLE) have a high level of kinin receptors as well as kallikrein, a kinin\u2010releasing enzyme, in the hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we evaluated the expression, distribution, and activity of <jats:styled-content style=\"fixed-case\">TOP<\/jats:styled-content> in the hippocampus of patients with <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content> and autopsy\u2010control tissues, through reverse\u2010transcription polymerase chain reaction (<jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR)<\/jats:styled-content>, enzymatic activity, Western blot, and immunohistochemistry. In addition, hippocampi of rats were analyzed using the pilocarpine\u2010induced epilepsy model. Animals were grouped according to the epilepsy phases defined in the model as acute, silent, and chronic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increased TOP <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression, decreased protein levels and enzymatic activity were observed in tissues of patients, compared to control samples. In addition, decreased TOP distribution was also visualized by immunohistochemistry. Similar results were observed in tissues of rats during the acute phase of epilepsy model. However, increased TOP <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression and no changes in immunoreactivity were found in the silent phase, whereas increased TOP <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression and increased enzymatic activity were observed in the chronic phase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The results show that these alterations could be related to a failure in the mechanisms involved in clearance of inflammatory peptides in the hippocampus, suggesting an accumulation of potentially harmful substances in nervous tissue such as A\u03b2, bradykinin, and antigenic peptides. These accumulations could be related to hippocampal inflammation observed in <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content> subjects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12606","type":"journal-article","created":{"date-parts":[[2014,4,4]],"date-time":"2014-04-04T18:37:22Z","timestamp":1396636642000},"page":"754-762","source":"Crossref","is-referenced-by-count":6,"title":["Expression and activity of thimet oligopeptidase (<scp>TOP<\/scp>) are modified in the hippocampus of subjects with temporal lobe epilepsy (<scp>TLE<\/scp>)"],"prefix":"10.1111","volume":"55","author":[{"given":"Priscila Santos Rodrigues","family":"Sim\u00f5es","sequence":"first","affiliation":[{"name":"Neurology\/Neurosurgery Department Federal University of S\u00e3o Paulo (UNIFESP) S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruna","family":"Visniauskas","sequence":"additional","affiliation":[{"name":"Psychobiology Department Federal University 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