{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:15:13Z","timestamp":1791407713904,"version":"4.3.3"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T00:00:00Z","timestamp":1487808000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007797","name":"Helsingin Yliopisto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007797","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Suomen Akatemia","doi-asserted-by":"publisher","award":["SA 259799"],"award-info":[{"award-number":["SA 259799"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004562","name":"Minist\u00e8re de l'Education Nationale, de l'Enseignement Superieur et de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004562","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Rewiring of excitatory glutamatergic neuronal circuits is a major abnormality in epilepsy. Besides the rewiring of excitatory circuits, an abnormal depolarizing \u03b3\u2010aminobutyric acidergic (GABAergic) drive has been hypothesized to participate in the epileptogenic processes. However, a remaining clinically relevant question is whether early post\u2013status epilepticus (SE) evoked chloride dysregulation is important for the remodeling of aberrant glutamatergic neuronal circuits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Osmotic minipumps were used to infuse intracerebrally a specific inhibitor of depolarizing GABAergic transmission as well as a functionally blocking antibody toward the pan\u2010neurotrophin receptor p75 (p75\n                      <jats:sup>NTR<\/jats:sup>\n                      ). The compounds were infused between 2 and 5 days after pilocarpine\u2010induced SE. Immunohistochemistry for NKCC1, KCC2, and ectopic recurrent mossy fiber (rMF) sprouting as well as telemetric electroencephalographic and electrophysiological recordings were performed at day 5 and 2 months post\u2010SE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Blockade of NKCC1 after SE with the specific inhibitor bumetanide restored NKCC1 and KCC2 expression, normalized chloride homeostasis, and significantly reduced the glutamatergic rMF sprouting within the dentate gyrus. This mechanism partially involves p75\n                      <jats:sup>NTR<\/jats:sup>\n                      signaling, as bumetanide application reduced SE\u2010induced p75\n                      <jats:sup>NTR<\/jats:sup>\n                      expression and functional blockade of p75\n                      <jats:sup>NTR<\/jats:sup>\n                      decreased rMF sprouting. The early transient (3 days) post\u2010SE infusion of bumetanide reduced rMF sprouting and recurrent seizures in the chronic epileptic phase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Our findings show that early post\u2010SE abnormal depolarizing GABA and p75\n                      <jats:sup>NTR<\/jats:sup>\n                      signaling fosters a long\u2010lasting rearrangement of glutamatergic network that contributes to the epileptogenic process. This finding defines promising and novel targets to constrain reactive glutamatergic network rewiring in adult epilepsy. Ann Neurol 2017;81:251\u2013265\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24870","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T03:35:13Z","timestamp":1484105713000},"page":"251-265","source":"Crossref","is-referenced-by-count":82,"title":["Depolarizing \u03b3\u2010aminobutyric acid contributes to glutamatergic network rewiring in epilepsy"],"prefix":"10.1002","volume":"81","author":[{"given":"Nazim","family":"Kourdougli","sequence":"first","affiliation":[{"name":"Inserm Unit 901 Inmed Marseille France"},{"name":"Mixed Unit of Research S901 Aix\u2010Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Inserm Unit 901 Inmed Marseille France"},{"name":"Mixed Unit of Research S901 Aix\u2010Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juho\u2010Matti","family":"Renko","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Pharmacotherapy University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Khirug","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Chazal","sequence":"additional","affiliation":[{"name":"Inserm Unit 901 Inmed Marseille France"},{"name":"Mixed Unit of Research S901 Aix\u2010Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina\u2010Kaisa","family":"Kukko\u2010Lukjanov","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari E.","family":"Lauri","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Luc","family":"Gaiarsa","sequence":"additional","affiliation":[{"name":"Inserm Unit 901 Inmed Marseille France"},{"name":"Mixed Unit of Research S901 Aix\u2010Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lique","family":"Peret","sequence":"additional","affiliation":[{"name":"Inserm Unit 901 Inmed Marseille France"},{"name":"Mixed Unit of Research S901 Aix\u2010Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eero","family":"Castr\u00e9n","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimo K.","family":"Tuominen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Pharmacotherapy University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Cr\u00e9pel","sequence":"additional","affiliation":[{"name":"Inserm Unit 901 Inmed Marseille France"},{"name":"Mixed Unit of Research S901 Aix\u2010Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Rivera","sequence":"additional","affiliation":[{"name":"Inserm Unit 901 Inmed Marseille France"},{"name":"Mixed Unit of Research S901 Aix\u2010Marseille University Marseille France"},{"name":"Neuroscience Center University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(07)63041-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32833749e4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2004.03.009"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2010.10.026"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3950"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.05-04-01016.1985"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90471-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00247950"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410260303"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-21-08523.2001"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2074-04.2004"},{"key":"e_1_2_7_13_1","author":"Lanerolle NC","year":"2012","journal-title":"Histopathology of human epilepsy"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.06.032"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-22-09754.2002"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.7869"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00239-2"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2045-04.2004"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602979103"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2761-07.2007"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4390-07.2007"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06863.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03247.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12620"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3282-11.2012"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0388-11.2011"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.04.019"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.07.004"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.03886.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19981215)54:6<734::AID-JNR2>3.0.CO;2-P"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20594"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2009.03.006"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1469-05.2005"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03086.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb13648.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0633-10.2010"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24124"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12424"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113618"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.085266"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.02.039"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990428)407:1<77::AID-CNE6>3.0.CO;2-S"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.11.012"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(07)63014-3"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2841-08.2008"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759091414552185"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2010.00011"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00299-6"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.04.019"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440609"},{"key":"e_1_2_7_51_1","volume-title":"Merritt's neurology","author":"Rowland LP","year":"2010"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.24870","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24870","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T13:44:25Z","timestamp":1695995065000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.24870"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1002\/ana.24870"],"URL":"https:\/\/doi.org\/10.1002\/ana.24870","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2]]}}}