{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:55:24Z","timestamp":1791312924676,"version":"4.3.1"},"reference-count":82,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RO1 NS083666"],"award-info":[{"award-number":["RO1 NS083666"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005191","name":"Craig H. 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We compared its effect with step\u2010training as it is known to improve spinal inhibition by restoring chloride homeostasis. In SCI rats, a prolonged bumetanide treatment increased postynaptic inhibition but not presynaptic inhibition of the plantar H\u2010reflex evoked by posterior biceps and semitendinosus (PBSt) group I afferents. By using <jats:italic>in vivo<\/jats:italic> intracellular recordings of motoneurons, we further show that a prolonged bumetanide increased postsynaptic inhibition by hyperpolarizing the reversal potential for inhibitory postsynaptic potentials (IPSPs) after SCI. However, in step\u2010trained SCI rats an acute delivery of bumetanide decreased presynaptic inhibition of the H\u2010reflex, but not postsynaptic inhibition. These results suggest that bumetanide might be a viable option to improve postsynaptic inhibition after SCI, but it also decreases the recovery of presynaptic inhibition with step\u2010training. We discuss whether the effects of bumetanide are mediated by NKCC1 or by off\u2010target effects.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15475-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>After spinal cord injury (SCI), chloride homeostasis is dysregulated over time in parallel with the decrease in presynaptic inhibition of Ia afferents and postsynaptic inhibition of motoneurons, and the development of spasticity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>While step\u2010training counteracts these effects, it cannot always be implemented in the clinic because of comorbidities. An alternative intervention is to use pharmacological strategies to decrease spasticity without hindering the recovery of motor function with step\u2010training.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here we found that, after SCI, a prolonged bumetanide (an FDA\u2010approved antagonist of the sodium\u2010potassium\u2010chloride intruder, NKCC1) treatment increases postsynaptic inhibition of the H\u2010reflex, and it hyperpolarizes the reversal potential for inhibitory postsynaptic potentials in motoneurons.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>However, in step\u2010trained SCI, an acute delivery of bumetanide decreases presynaptic inhibition of the H\u2010reflex, but not postsynaptic inhibition.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results suggest that bumetanide has the potential to decrease spastic symptoms related to a decrease in postsynaptic but not presynaptic inhibition after SCI.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp283753","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T12:09:35Z","timestamp":1677499775000},"page":"1425-1447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bumetanide increases postsynaptic inhibition after chronic SCI and decreases presynaptic inhibition with step\u2010training"],"prefix":"10.1113","volume":"601","author":[{"given":"Guillaume","family":"Caron","sequence":"first","affiliation":[{"name":"Marion Murray Spinal Cord Research Center, Department of Neurobiology and Anatomy Drexel University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9893-1334","authenticated-orcid":false,"given":"Jadwiga","family":"Bilchak","sequence":"additional","affiliation":[{"name":"Marion Murray Spinal Cord Research 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