{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:55:20Z","timestamp":1791312920980,"version":"4.3.1"},"reference-count":36,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T00:00:00Z","timestamp":1555027200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p>Spasticity after spinal cord injury has considerable quality of life implications, impacts on rehabilitation efforts and necessitates long-term multi-disciplinary pharmacological and non-pharmacological management. The potassium chloride co-transporter (KCC2) plays a central role in intracellular chloride homeostasis and the inhibitory function of mature neurons. Animal studies consistently have demonstrated a downregulation of KCC2 activity after spinal cord transection, causing a shift from the inhibitory action of gamma-aminobutyric acid and glycine to an excitatory effect. Furosemide, a recognized KCC2 antagonist in animals, blocks the formation of inhibitory post-synaptic potentials in spinal motoneurons without affecting excitatory post-synaptic potentials. Based on observations in animals studies, we hypothesized that furosemide may be used to unmask KCC2 downregulation after spinal cord injury in humans, which contributes to reflex hyperexcitability. We have shown previously that furosemide reduces both pre-synaptic and post-synaptic inhibition in healthy subjects without altering monosynaptic excitatory transmission. These findings provide evidence that furosemide may be used in humans to evaluate inhibitory synapses in the spinal cord. In this present study, we show that furosemide fails to modulate both pre- and post-synaptic inhibitions relayed to soleus spinal motor neurons in persons with spinal cord injury. The lack of furosemide effect after spinal cord injury suggests KCC2 dysfunction in humans, resulting in reduced inhibitory synaptic transmission in spinal neurons. Our findings suggest that KCC2 dysfunction may be an important etiological factor in hyperreflexia after spinal cord injury. These observations may pave the way to novel therapeutic strategies against spasticity centered on chloride homeostasis.<\/jats:p>","DOI":"10.1089\/neu.2017.5560","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T06:03:39Z","timestamp":1542002619000},"page":"1469-1477","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Furosemide Unmasks Inhibitory Dysfunction after Spinal Cord Injury in Humans: Implications for Spasticity"],"prefix":"10.1177","volume":"36","author":[{"given":"Wanalee","family":"Klomjai","sequence":"first","affiliation":[{"name":"Faculty of Physical Therapy, Mahidol University, Nakonpathom, Thailand."}],"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, Garches, France; Univ. 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