{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T02:26:22Z","timestamp":1788834382383,"version":"build-2803163510"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["460333672 CRC1540 EBM"],"award-info":[{"award-number":["460333672 CRC1540 EBM"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Temporal lobe epilepsy is the most prevalent form of drug-resistant focal epilepsy and is frequently associated with neuronal cell loss and astrogliosis in the hippocampus, i.e. hippocampal sclerosis (HS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we performed mass spectrometry-based proteomic profiling of microdissected hippocampal, neocortical, and white matter tissue obtained from TLE patients and respective control samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In hippocampal TLE tissue, we observed significant upregulation of proteins involved in complement system activation, extracellular matrix (ECM) organization, and astrocyte reactivity, indicative of active inflammatory remodeling within the sclerotic hippocampus. Conversely, synaptic proteins, including glutamate and gamma-aminobutyric acid (GABA) receptors, along with other regulators of synaptic structure and function, were markedly downregulated. Interestingly, in neocortical and white matter regions from the same TLE patients, immune- and ECM-related proteins were downregulated or unchanged, whereas synaptic proteins were preserved or upregulated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These region-specific molecular signatures suggest that inflammatory-driven ECM remodeling is spatially restricted to the epileptogenic hippocampus, where it may contribute to synaptic destabilization and network dysfunction. Together, our findings support the hypothesis that inflammatory ECM remodeling in the hippocampus plays a central role in epileptogenesis in TLE. In contrast, the neocortical and white matter regions may undergo compensatory adaptions. The convergence of immune and ECM-related alterations on synaptic structures highlights a potential pathophysiological axis in epilepsy and points to novel molecular targets for therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2026.1728666","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:40:43Z","timestamp":1771569643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Temporal lobe epilepsy is associated with neuroinflammation, extracellular matrix remodeling, and synaptic protein alterations"],"prefix":"10.3389","volume":"19","author":[{"given":"Sophia","family":"Auer","sequence":"first","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, University Hospital Erlangen and FAU Erlangen-N\u00fcrnberg (European Reference Network (ERN) EpiCARE)","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schicht","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingmar","family":"Bl\u00fcmcke","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, University Hospital Erlangen and FAU Erlangen-N\u00fcrnberg (European Reference Network (ERN) EpiCARE)","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"749","DOI":"10.5137\/1019-5149.JTN.10738-14.0","article-title":"Increased expression of matrix metalloproteinase-9 in patients with temporal lobe epilepsy","volume":"25","author":"Acar","year":"2015","journal-title":"Turk. 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