{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:00:03Z","timestamp":1792112403944,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HA7597\/1\u20101"],"award-info":[{"award-number":["HA7597\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hippocampus"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hippocampal sclerosis (HS) in Temporal Lobe Epilepsy (TLE) shows neuronal death in cornu ammonis (CA)1, CA3, and CA4. It is known that granule cells and CA2 neurons survive and their axons, the mossy fibers (MF), lose their target cells in CA3 and CA4 and sprout to the granule cell layer and molecular layer. We examined in TLE patients and in a mouse epilepsy model, whether MF sprouting is directed to the dentate gyrus or extends to distant CA regions and whether sprouting is associated with death of target neurons in CA3 and CA4. In 319 TLE patients, HS was evaluated by Wyler grade and International League against Epilepsy (ILAE) types using immunohistochemistry against neuronal nuclei (NeuN). Synaptoporin was used to colocalize MF. In addition, transgenic Thy1\u2010eGFP mice were intrahippocampally injected with kainate and sprouting of eGFP\u2010positive MFs was analyzed together with immunocytochemistry for regulator of G\u2010protein signaling 14 (RGS14). In human HS Wyler III and IV as well as in ILAE 1, 2, and 3 specimens, we found synaptoporin\u2010positive axon terminals in CA2 and even in CA1, associated with the extent of granule cell dispersion. Sprouting was seen in cases with cell death of target neurons in CA3 and CA4 (classical severe HS ILAE type 1) but also without this cell death (atypical HS ILAE type 2). Similarly, in epileptic mice eGFP\u2010positive MFs sprouted to CA2 and beyond. The presence of MF terminals in the CA2 pyramidal cell layer and in CA1 was also correlated with the extent of granule cell dispersion. The similarity of our findings in human specimens and in the mouse model highlights the importance and opens up new chances of using translational approaches to determine mechanisms underlying TLE.<\/jats:p>","DOI":"10.1002\/hipo.23323","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T08:08:11Z","timestamp":1615795691000},"page":"580-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Mossy fiber sprouting into the hippocampal region\n                    <scp>CA2<\/scp>\n                    in patients with temporal lobe epilepsy"],"prefix":"10.1002","volume":"31","author":[{"given":"Thomas M.","family":"Freiman","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Rostock University Medical Center Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"H\u00e4ussler","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Experimental Epilepsy Research Medical Center\u2014University of Freiburg, Faculty of Medicine Freiburg Germany"},{"name":"Faculty of Medicine, Center for Basics in NeuroModulation University of Freiburg Freiburg Germany"},{"name":"BrainLinks\u2010BrainTools Center University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Zentner","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Neurosurgery Medical Center\u2014University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soroush","family":"Doostkam","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Neuropathology Medical Center\u2014University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Beck","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Neurosurgery Medical Center\u2014University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Scheiwe","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Neurosurgery Medical Center\u2014University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Brandt","sequence":"additional","affiliation":[{"name":"Epilepsy Center University Medical Center, Albert\u2010Ludwigs\u2010University Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola A.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Experimental Epilepsy Research Medical Center\u2014University of Freiburg, Faculty of Medicine Freiburg Germany"},{"name":"Faculty of Medicine, Center for Basics in NeuroModulation University of Freiburg Freiburg Germany"},{"name":"BrainLinks\u2010BrainTools Center University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5171-6373","authenticated-orcid":false,"given":"Barbara","family":"Puhahn\u2010Schmeiser","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Neurosurgery Medical Center\u2014University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.11.024"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70175-3"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0187-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb01577.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12220"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1750-3639.2002.tb00436.x","article-title":"Ammon's horn sclerosis: A maldevelopmental disorder associated with temporal lobe epilepsy","volume":"12","author":"Blumcke I.","year":"2002","journal-title":"Brain Pathology"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00305720"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00223955"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-81522-5"},{"key":"e_1_2_11_11_1","first-page":"609","volume-title":"Outcome with respect to epileptic seizures in surgical treatment of the epilepsies","author":"Engel J. 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