{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:11:38Z","timestamp":1791263498108,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2014,6,3]],"date-time":"2014-06-03T00:00:00Z","timestamp":1401753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"ANR","award":["FIHSC 2013-2014"],"award-info":[{"award-number":["FIHSC 2013-2014"]}]},{"name":"APHP","award":["Hemipleg P070804"],"award-info":[{"award-number":["Hemipleg P070804"]}]},{"DOI":"10.13039\/501100004792","name":"MESR","doi-asserted-by":"crossref","award":["Er 6 UPMC"],"award-info":[{"award-number":["Er 6 UPMC"]}],"id":[{"id":"10.13039\/501100004792","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CICIT","award":["805"],"award-info":[{"award-number":["805"]}]},{"name":"post-doctoral fellowship from FRM","award":["SPF20101221068"],"award-info":[{"award-number":["SPF20101221068"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>It has been demonstrated in humans that furosemide crosses the blood\u2013brain barrier and blocks activity in the epileptic brain.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In this study, we demonstrated using non\u2010invasive electrophysiological techniques in healthy human subjects that furosemide, a cation\u2010chloride co\u2010transporter blocker, orally administered at doses commonly used in the clinic (40\u00a0mg), reduces the efficacy of pre\u2010 and postsynaptic inhibition of soleus motoneurons in the spinal cord.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Furosemide can be a useful tool to detect the intrinsic functioning of inhibitory synapses and to explore if the reduced inhibitory interneuronal activity that probably contributes to spasticity also exists in humans with spinal cord injury.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>During neural development in animals, GABAergic and glycinergic neurons are first excitatory, and then become inhibitory in the mature state. This developmental shift is due mainly to strong expression of the cation\u2010chloride K\u2013Cl cotransporter 2 (KCC2) and down\u2010regulation of Na\u2013K\u2013Cl cotransporter 1 (NKCC1) during maturation. The down\u2010regulation of co\u2010transporter KCC2 after spinal cord transection in animals leads to the depolarising (excitatory) action of GABA and glycine and thus results in a reduction of inhibitory synaptic efficiency. Furosemide, a loop diuretic, has been shown to selectively and reversibly block inhibitory postsynaptic potentials without affecting excitatory postsynaptic potentials in animal spinal neurons. Moreover, this diuretic has been also demonstrated to block the cation\u2010chloride co\u2010transporters. Here, we used furosemide to demonstrate changes in spinal inhibitory networks in healthy human subjects. Non\u2010invasive electrophysiological techniques were used to assess presynaptic inhibition, postsynaptic inhibition and the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons in the spinal cord. Orally administered furosemide, at doses commonly used in the clinic (40\u00a0mg), significantly reduced spinal inhibitory interneuronal activity for at least 70\u00a0min from intake compared to control experiments in the same subjects while no changes were observed in the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons. The reduction of inhibition was dose\u2010dependent. Our results provide indirect evidence that reversible changes in the cation\u2010chloride transport system induce modulations of inhibitory neuronal activity at spinal cord level in humans.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2013.265314","type":"journal-article","created":{"date-parts":[[2014,5,16]],"date-time":"2014-05-16T10:08:35Z","timestamp":1400234915000},"page":"2865-2879","source":"Crossref","is-referenced-by-count":6,"title":["Changes in spinal inhibitory networks induced by furosemide in humans"],"prefix":"10.1113","volume":"592","author":[{"given":"Wanalee","family":"Klomjai","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9s UPMC Univ Paris 06 ER 6: Physiologie et physiopathologie de la motricit\u00e9 chez l\u2019Homme M\u00e9decine Physique et R\u00e9adaptation H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  75013 Paris France"},{"name":"Faculty of Physical Therapy Mahidol University  73170 Nakonpathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Lackmy\u2010Vall\u00e9e","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s UPMC Univ Paris 06 ER 6: Physiologie et physiopathologie de la motricit\u00e9 chez l\u2019Homme M\u00e9decine Physique et R\u00e9adaptation H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  75013 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Katz","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s UPMC Univ Paris 06 ER 6: Physiologie et physiopathologie de la motricit\u00e9 chez l\u2019Homme M\u00e9decine Physique et R\u00e9adaptation H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  75013 Paris France"},{"name":"APHP Service de M\u00e9dicine Physique et R\u00e9adaptation H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, 75651  Paris Cedex 13 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Bussel","sequence":"additional","affiliation":[{"name":"APHP Service de M\u00e9decine Physique et R\u00e9adaptation H\u00f4pital Raymond Poincar\u00e9  92380 Garches France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djamel","family":"Bensmail","sequence":"additional","affiliation":[{"name":"APHP Service de M\u00e9decine Physique et R\u00e9adaptation H\u00f4pital Raymond Poincar\u00e9  92380 Garches France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Charles","family":"Lamy","sequence":"additional","affiliation":[{"name":"CESEM, CNRS UMR 8194 Universit\u00e9 Paris Descartes  75006 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Roche","sequence":"additional","affiliation":[{"name":"APHP Service de M\u00e9decine Physique et R\u00e9adaptation H\u00f4pital Raymond Poincar\u00e9  92380 Garches France"},{"name":"Universit\u00e9 Versailles\u2010Saint\u2010Quentin EA 4497  92380 Garches France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.8.1688"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016726"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2107"},{"key":"e_1_2_6_6_1","first-page":"442P","article-title":"Pharmacokinetics of frusemide related to diuretic response [proceedings]","volume":"57","author":"Branch RA","year":"1976","journal-title":"Br J Pharmacol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1977.tb00682.x"},{"key":"e_1_2_6_8_1","volume-title":"Brain Function","author":"Brazier MAB","year":"1961"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018393"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00230098"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00230683"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/2151502a0"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2012.07.013"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.35.2.234"},{"key":"e_1_2_6_15_1","first-page":"943","article-title":"Studies of spasticity in man. 4. 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