{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:42:32Z","timestamp":1792226552888,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The extracellular matrix (ECM) performs several functions during development and in mature nervous tissue plasticity; ECM concentrates in lattice\u2010like envelopes called perineuronal nets (PNNs), which surround the cell bodies and proximal dendrites, mainly of parvalbumin (PV) \u03b3\u2010aminobutyric acidergic interneurons. PNNs are proposed to serve synaptic plasticity regulation, synapse stabilization, and neuron protection, by forming a physical barrier from potentially damaging neurochemical stimuli. We analyzed aggrecan expression, a major component of adult PNNs, in human specimens obtained from epilepsy surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Postsurgical tissues were obtained from 20 patients with drug\u2010resistant epilepsy: six cases with no histological alterations (cryptogenic epilepsy) and 14 patients showing type IIa and IIb focal cortical dysplasia (FCDII). For comparison, cortices from three autoptic controls with short postmortem delay were analyzed. Immunohistochemistry, confocal microscopy, and RNAscope technique were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Control autoptic cases showed high aggrecan expression in the cortex, with a clear decreasing expression gradient from occipital to frontal and temporal areas. This expression gradient was lost in cryptogenic cases, which showed severe aggrecan loss, with residual immunoreactive arrangements mainly around PV interneurons. In FCDII, altered immunolabeling was evident in the core of the dysplastic lesion, and PNNs were identified around both PV interneurons and dysmorphic neurons (DNs) presenting abnormal vGLUT1 and vGAT perisomatic basket formations. Diffuse weak staining of the white matter without PNNs was also found in FCDII. As for cryptogenic cases, FCDII perilesional cortex showed a marked aggrecan staining loss. RNAscope findings confirmed that aggrecans are produced by FCDII pathological neurons, such as DNs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These data support the notion that etiology\u2010specific PNN remodeling is part of the epileptogenic process. FCDII tissues show altered PNN expression in DNs suggestive of a pathogenic role within the FCD lesion, and the disappearance of histochemical PNN labeling in cryptogenic and FCDII perilesional area suggests a possible role mediated by seizure activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70368","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:03:39Z","timestamp":1782853419000},"page":"5547-5559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Perineuronal net abnormalities in epileptic human tissue"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-2067","authenticated-orcid":false,"given":"Dalia","family":"De Santis","sequence":"first","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan 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