{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T16:28:01Z","timestamp":1794414481915,"version":"4.9.1"},"reference-count":148,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22521104"],"award-info":[{"award-number":["22521104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170406"],"award-info":[{"award-number":["82170406"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970238"],"award-info":[{"award-number":["81970238"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology &amp; Therapeutics"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.pharmthera.2026.109129","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:52:26Z","timestamp":1791269546000},"page":"109129","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Targeting KCC2 and NKCC1 for spinal motor dysfunction: pharmacology, therapeutic opportunities, and translational roadmap"],"prefix":"10.1016","volume":"288","author":[{"given":"Jinwei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris S.","family":"Shenkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pharmthera.2026.109129_bb0005","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0172-19.2019","article-title":"Removal of the potassium chloride co-transporter from the somatodendritic membrane of axotomized motoneurons is independent of BDNF\/TrkB signaling but is controlled by neuromuscular innervation","volume":"6","author":"Akhter","year":"2019","journal-title":"eNeuro"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0010","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/0014-4886(87)90225-1","article-title":"Electromyography of rat soleus, medical gastrocnemius, and tibialis anterior during hind limb suspension","volume":"96","author":"Alford","year":"1987","journal-title":"Experimental Neurology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0015","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1046\/j.1460-9568.2002.02006.x","article-title":"Intrinsic optical signals in the dorsal horn of rat spinal cord slices elicited by brief repetitive stimulation","volume":"15","author":"Asai","year":"2002","journal-title":"European Journal of Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0020","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1213\/ANE.0b013e31822e0a5d","article-title":"Inhibition of KCC2 in mouse spinal cord neurons leads to hypersensitivity to thermal stimulation","volume":"113","author":"Austin","year":"2011","journal-title":"Anesthesia and Analgesia"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0025","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.nbd.2016.02.014","article-title":"Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures","volume":"91","author":"Awad","year":"2016","journal-title":"Neurobiology of Disease"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0030","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.3390\/cells11061052","article-title":"Silencing of Ago-2 interacting protein SERBP1 relieves KCC2 repression by miR-92 in neurons","volume":"11","author":"Barbato","year":"2022","journal-title":"Cells"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0035","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1093\/brain\/awae126","article-title":"Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer\u2019s disease and 5XFAD mice","volume":"147","author":"Barbour","year":"2024","journal-title":"Brain"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0040","doi-asserted-by":"crossref","first-page":"12898","DOI":"10.1523\/JNEUROSCI.1552-13.2013","article-title":"Selective effects of baclofen on use-dependent modulation of GABAB inhibition after tetraplegia","volume":"33","author":"Barry","year":"2013","journal-title":"Journal of Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0045","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1161\/STROKEAHA.115.008939","article-title":"Inhibition of WNK3 Kinase signaling reduces brain damage and accelerates neurological recovery after stroke","volume":"46","author":"Begum","year":"2015","journal-title":"Stroke"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0050","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2025.115401","article-title":"Hyperreflexia after corticospinal tract lesion reflects 1 A afferent circuit changes not increased KCC2 hyperexcitability","volume":"394","author":"Bethea","year":"2025","journal-title":"Experimental Neurology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0055","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1089\/neu.2019.6526","article-title":"Rehabilitation decreases spasticity by restoring chloride homeostasis through the brain-derived neurotrophic factor-KCC2 pathway after spinal cord injury","volume":"37","author":"Beverungen","year":"2020","journal-title":"Journal of Neurotrauma"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuint.2022.105441","article-title":"Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice","volume":"162","author":"Bhuiyan","year":"2023","journal-title":"Neurochemistry International"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0065","doi-asserted-by":"crossref","DOI":"10.1111\/cns.14654","article-title":"SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia","volume":"30","author":"Bhuiyan","year":"2024","journal-title":"CNS Neuroscience & Therapeutics"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0070","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1161\/STROKEAHA.121.038351","article-title":"NF-kappaB signaling-mediated activation of WNK-SPAK-NKCC1 cascade in worsened stroke outcomes of Ang II-hypertensive mice","volume":"53","author":"Bhuiyan","year":"2022","journal-title":"Stroke"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0075","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.3390\/ijms22094858","article-title":"Exercise-induced plasticity in signaling pathways involved in motor recovery after spinal cord injury","volume":"22","author":"Bilchak","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0080","doi-asserted-by":"crossref","first-page":"5701","DOI":"10.1113\/JP287774","article-title":"KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury","volume":"603","author":"Bilchak","year":"2025","journal-title":"The Journal of Physiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2021.113605","article-title":"Enhancing KCC2 activity decreases hyperreflexia and spasticity after chronic spinal cord injury","volume":"338","author":"Bilchak","year":"2021","journal-title":"Experimental Neurology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0090","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1073\/pnas.1213680110","article-title":"Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2","volume":"110","author":"Bos","year":"2013","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0095","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nm.2107","article-title":"Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury","volume":"16","author":"Boulenguez","year":"2010","journal-title":"Nature Medicine"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.jchemneu.2020.101847","article-title":"Differential effects of spinal cord transection on glycinergic and GABAergic synaptic signaling in sub-lesional lumbar motoneurons","volume":"113","author":"Bras","year":"2021","journal-title":"Journal of Chemical Neuroanatomy"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0105","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25189942","article-title":"VEGF, but Not BDNF, prevents the downregulation of KCC2 induced by axotomy in extraocular motoneurons","volume":"25","author":"Capilla-Lopez","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0110","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/nm.4442","article-title":"The small molecule CLP257 does not modify activity of the K+\u2013Cl\u2212 co-transporter KCC2 but does potentiate GABAA receptor activity","volume":"23","author":"Cardarelli","year":"2017","journal-title":"Nature Medicine"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0115","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1113\/JP283753","article-title":"Bumetanide increases postsynaptic inhibition after chronic SCI and decreases presynaptic inhibition with step-training","volume":"601","author":"Caron","year":"2023","journal-title":"The Journal of Physiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0120","doi-asserted-by":"crossref","first-page":"11987","DOI":"10.1038\/s41598-018-30486-7","article-title":"Dose-dependent reversal of KCC2 hypofunction and phenobarbital-resistant neonatal seizures by ANA12","volume":"8","author":"Carter","year":"2018","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0125","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41598-017-00196-7","article-title":"KCC2 downregulation facilitates epileptic seizures","volume":"7","author":"Chen","year":"2017","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0130","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.ibneur.2022.04.010","article-title":"Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus","volume":"12","author":"Chen","year":"2022","journal-title":"IBRO Neuroscience Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0135","article-title":"VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia","volume":"122","author":"Chen","year":"2025","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0140","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1111\/epi.17097","article-title":"Global transgenic upregulation of KCC2 confers enhanced diazepam efficacy in treating sustained seizures","volume":"63","author":"Cheung","year":"2022","journal-title":"Epilepsia"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0145","doi-asserted-by":"crossref","first-page":"7871","DOI":"10.1038\/s41598-023-34701-y","article-title":"KCC2 downregulation after sciatic nerve injury enhances motor function recovery","volume":"13","author":"Cheung","year":"2023","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0150","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1152\/jn.00550.2014","article-title":"Serotonin receptor and KCC2 gene expression in lumbar flexor and extensor motoneurons posttransection with and without passive cycling","volume":"113","author":"Chopek","year":"2015","journal-title":"Journal of Neurophysiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0155","doi-asserted-by":"crossref","first-page":"8976","DOI":"10.1523\/JNEUROSCI.0678-14.2014","article-title":"Exercise modulates chloride homeostasis after spinal cord injury","volume":"34","author":"Cote","year":"2014","journal-title":"Journal of Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0160","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/nature01868","article-title":"Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain","volume":"424","author":"Coull","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0165","doi-asserted-by":"crossref","DOI":"10.1186\/1744-8069-4-36","article-title":"The role of cation-dependent chloride transporters in neuropathic pain following spinal cord injury","volume":"4","author":"Cramer","year":"2008","journal-title":"Molecular Pain"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0170","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/brain\/awz105","article-title":"Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing","volume":"142","author":"Dedek","year":"2019","journal-title":"Brain"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0175","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.expneurol.2006.04.021","article-title":"Soleus motoneuron excitability after rat hindlimb unloading using histology and a new electrophysiological approach to record a neurographic analogue of the H-reflex","volume":"201","author":"Dedoncker","year":"2006","journal-title":"Experimental Neurology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0180","doi-asserted-by":"crossref","DOI":"10.1177\/17590914221093257","article-title":"KCC2 rs2297201 gene polymorphism might be a predictive genetic marker of febrile seizures","volume":"14","author":"Dimitrijevic","year":"2022","journal-title":"ASN Neuro"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0185","article-title":"Enhancing KCC2 function reduces interictal activity and prevents seizures in temporal lobe epilepsy","volume":"123","author":"Donneger","year":"2026","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0190","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1002\/cne.25395","article-title":"Small sensory spinal lesions that affect hand function in monkeys greatly alter primary afferent and motor neuron connections in the cord","volume":"530","author":"Fisher","year":"2022","journal-title":"Journal of Comparative Neurology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0195","doi-asserted-by":"crossref","first-page":"ra65","DOI":"10.1126\/scisignal.aaa0354","article-title":"WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons","volume":"8","author":"Friedel","year":"2015","journal-title":"Science Signaling"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0200","first-page":"777","article-title":"Effects of high frequency repetitive transcranial magnetic stimulation on KCC2 expression in rats with spasticity following spinal cord injury","volume":"37","author":"Gao","year":"2017","journal-title":"Journal of Huazhong University of Science and Technology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0205","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adp1873","article-title":"Neuronal HDAC3 knockdown promotes propriospinal detour pathway formation and locomotor recovery in a mouse model of spinal cord injury","volume":"17","author":"Gao","year":"2025","journal-title":"Science Translational Medicine"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0210","doi-asserted-by":"crossref","first-page":"14020","DOI":"10.1074\/jbc.M900142200","article-title":"The Ste20 kinases Ste20-related proline-alanine-rich kinase and oxidative-stress response 1 regulate NKCC1 function in sensory neurons","volume":"284","author":"Geng","year":"2009","journal-title":"Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0215","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1152\/japplphysiol.00997.2015","article-title":"Hindlimb unloading: rodent analog for microgravity","volume":"120","author":"Globus","year":"2016","journal-title":"Journal of Applied Physiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0220","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2025.113489","article-title":"Therapeutic potential of 5HT2CR in alleviating spasticity and pain via modulation of motor neurons and interneurons in spinal cord injury","volume":"28","author":"Gong","year":"2025","journal-title":"iScience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0225","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/s40478-025-02137-2","article-title":"Pharmacological inhibition of SPAK-NKCC1 complex attenuates astrogliosis and restores cerebral blood flow in a mouse model of VCID","volume":"13","author":"Habib","year":"2025","journal-title":"Acta Neuropathologica Communications"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0230","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1002\/epi.70258","article-title":"Compound heterozygous SLC12A5 variants expand the molecular and functional spectrum of KCC2-developmental and epileptic encephalopathy","volume":"67","author":"Hamze","year":"2026","journal-title":"Epilepsia"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0235","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/j.1749-6632.2010.05462.x","article-title":"Role of NKCC1 and KCC2 in the development of chronic neuropathic pain following spinal cord injury","volume":"1198","author":"Hasbargen","year":"2010","journal-title":"Annals of the New York Academy of Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0240","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.nbd.2011.01.001","article-title":"Increase in BDNF-mediated TrkB signaling promotes epileptogenesis in a mouse model of mesial temporal lobe epilepsy","volume":"42","author":"Heinrich","year":"2011","journal-title":"Neurobiology of Disease"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0245","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.1073\/pnas.0909032107","article-title":"Molecular components of signal amplification in olfactory sensory cilia","volume":"107","author":"Hengl","year":"2010","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0250","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s40478-019-0852-x","article-title":"KCC2 expression levels are reduced in post mortem brain tissue of Rett syndrome patients","volume":"7","author":"Hinz","year":"2019","journal-title":"Acta Neuropathologica Communications"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0255","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s40478-026-02257-3","article-title":"Temporal and cell-type specific SPAK-NKCC1 disruption following severe TBI in the developing gyrencephalic brain","volume":"14","author":"Hochstetler","year":"2026","journal-title":"Acta Neuropathologica Communications"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0260","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/s41593-023-01290-y","article-title":"Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus","volume":"26","author":"Hu","year":"2023","journal-title":"Nature Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0265","first-page":"1236","article-title":"A case of Gitelman syndrome with physical retardation","volume":"42","author":"Huang","year":"2017","journal-title":"Zhong Nan Da Xue Xue Bao. Yi Xue Ban"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0270","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.expneurol.2016.09.005","article-title":"Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization","volume":"285","author":"Huang","year":"2016","journal-title":"Experimental Neurology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0275","article-title":"Piezo1 dictates K(+) homeostasis through coordinated regulation of the ubiquitin ligase Kelch-like 3 in RBCs and the kidney","volume":"123","author":"Ishizawa","year":"2026","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0280","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2023.100957","article-title":"Direct activation of KCC2 arrests benzodiazepine refractory status epilepticus and limits the subsequent neuronal injury in mice","volume":"4","author":"Jarvis","year":"2023","journal-title":"Cell Reports Medicine"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0285","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.114001","article-title":"Trifluoro-icaritin ameliorates spared nerve injury-induced neuropathic pain by inhibiting microglial activation through alpha7nAChR-mediated blockade of BDNF\/TrkB\/KCC2 signaling in the spinal cord of rats","volume":"157","author":"Jia","year":"2023","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0290","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2513155122","article-title":"Activation of WNK1 signaling through Piezo1","volume":"122","author":"Jung","year":"2025","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0295","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1152\/jn.00865.2015","article-title":"Kinase-KCC2 coupling: Cl- rheostasis, disease susceptibility, therapeutic target","volume":"115","author":"Kahle","year":"2016","journal-title":"Journal of Neurophysiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0300","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1001\/jamaneurol.2014.21","article-title":"Therapeutic restoration of spinal inhibition via druggable enhancement of potassium-chloride cotransporter KCC2-mediated chloride extrusion in peripheral neuropathic pain","volume":"71","author":"Kahle","year":"2014","journal-title":"JAMA Neurology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0305","doi-asserted-by":"crossref","first-page":"766","DOI":"10.15252\/embr.201438840","article-title":"Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy","volume":"15","author":"Kahle","year":"2014","journal-title":"EMBO Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0310","doi-asserted-by":"crossref","first-page":"ra32","DOI":"10.1126\/scisignal.aad0163","article-title":"Inhibition of the kinase WNK1\/HSN2 ameliorates neuropathic pain by restoring GABA inhibition","volume":"9","author":"Kahle","year":"2016","journal-title":"Science Signaling"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0315","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.3390\/life11111161","article-title":"Prochlorperazine withdraws the delayed onset tonic activity of unloaded rat soleus muscle: A pilot study","volume":"11","author":"Kalashnikov","year":"2021","journal-title":"Life"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0320","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1111\/ejn.13094","article-title":"Acute TrkB inhibition rescues phenobarbital-resistant seizures in a mouse model of neonatal ischemia","volume":"42","author":"Kang","year":"2015","journal-title":"European Journal of Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0325","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.ymthe.2024.01.029","article-title":"Knockdown of calpain1 in lumbar motoneurons reduces spasticity after spinal cord injury in adult rats","volume":"32","author":"Kerzonkuf","year":"2024","journal-title":"Molecular Therapy"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0330","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0330600","article-title":"Scorpion (Hottentotta tamulus) venom pre-exposure delays functional recovery in mice following peripheral nerve injury","volume":"20","author":"Khan","year":"2025","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0335","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.136007","article-title":"TrkB agonists prevent postischemic emergence of refractory neonatal seizures in mice","volume":"5","author":"Kipnis","year":"2020","journal-title":"JCI Insight"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0340","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1089\/neu.2017.5560","article-title":"Furosemide unmasks inhibitory dysfunction after spinal cord injury in humans: Implications for spasticity","volume":"36","author":"Klomjai","year":"2019","journal-title":"Journal of Neurotrauma"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0345","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2025.108399","article-title":"Inefficient maturation of disease-linked mutant forms of the KCC2 potassium-chloride cotransporter correlates with predicted pathogenicity","volume":"301","author":"Kok","year":"2025","journal-title":"Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0350","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1016\/j.gim.2022.05.009","article-title":"Rare pathogenic variants in WNK3 cause X-linked intellectual disability","volume":"24","author":"Kury","year":"2022","journal-title":"Genetics in Medicine"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0355","doi-asserted-by":"crossref","first-page":"17985","DOI":"10.1074\/jbc.M702664200","article-title":"Biological cross-talk between WNK1 and the transforming growth factor beta-Smad signaling pathway","volume":"282","author":"Lee","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0360","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nn.2806","article-title":"NMDA receptor activity downregulates KCC2 resulting in depolarizing GABAA receptor-mediated currents","volume":"14","author":"Lee","year":"2011","journal-title":"Nature Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0365","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.spinee.2013.06.100","article-title":"Persistent phosphorylation of NKCC1 and WNK1 in the epicenter of the spinal cord following contusion injury","volume":"14","author":"Lee","year":"2014","journal-title":"The Spine Journal"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0370","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1093\/brain\/awab343","article-title":"Inhibiting with-no-lysine kinases enhances K+\/Cl\u2212 cotransporter 2 activity and limits status epilepticus","volume":"145","author":"Lee","year":"2022","journal-title":"Brain"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0375","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.neuint.2019.04.003","article-title":"Role of the BDNF-TrkB pathway in KCC2 regulation and rehabilitation following neuronal injury: A mini review","volume":"128","author":"Lee-Hotta","year":"2019","journal-title":"Neurochemistry International"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0380","doi-asserted-by":"crossref","first-page":"e1056","DOI":"10.1038\/tp.2017.10","article-title":"Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders","volume":"7","author":"Lemonnier","year":"2017","journal-title":"Translational Psychiatry"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0385","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1089\/neu.2022.0318","article-title":"Inhibition of HMGB1 attenuates spinal cord edema by reducing the expression of Na+-K+-Cl- Cotransporter-1 and Na+\/H+ Exchanger-1 in both astrocytes and endothelial cells after spinal cord injury in rats","volume":"40","author":"Li","year":"2023","journal-title":"Journal of Neurotrauma"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0390","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1007\/s11064-022-03561-9","article-title":"Body weight-supported treadmill training ameliorates motoneuronal hyperexcitability by increasing GAD-65\/67 and KCC2 expression via TrkB signaling in rats with incomplete spinal cord injury","volume":"47","author":"Li","year":"2022","journal-title":"Neurochemical Research"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0395","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1089\/neu.2017.5152","article-title":"Prochlorperazine increases KCC2 function and reduces spasticity after spinal cord injury","volume":"34","author":"Liabeuf","year":"2017","journal-title":"Journal of Neurotrauma"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0400","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/6659668","article-title":"LIFU alleviates neuropathic pain by improving the KCC(2) expression and inhibiting the CaMKIV-KCC(2) pathway in the L4-L5 section of the spinal cord","volume":"2021","author":"Liao","year":"2021","journal-title":"Neural Plasticity"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0405","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/ner.12927","article-title":"Chronic electrical stimulation reduces hyperalgesia and associated spinal changes induced by peripheral nerve injury","volume":"22","author":"L\u00f3pez-\u00c1lvarez","year":"2019","journal-title":"Neuromodulation: Technology at the Neural Interface"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0410","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1097\/CCM.0B013E31816590C4","article-title":"NKCC1-mediated traumatic brain injury-induced brain edema and neuron death via Raf\/MEK\/MAPK cascade","volume":"36","author":"Lu","year":"2008","journal-title":"Critical Care Medicine"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0415","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2021.174205","article-title":"BDNF modulated KCC2 ubiquitylation in spinal cord dorsal horn of mice","volume":"906","author":"Ma","year":"2021","journal-title":"European Journal of Pharmacology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0420","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1113\/JP287100","article-title":"Transcutaneous spinal cord stimulation at alternating intensities preferentially prevents the development of spasticity after contusion SCI in rat","volume":"603","author":"Malloy","year":"2025","journal-title":"The Journal of Physiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0425","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2024.114754","article-title":"Multi-session transcutaneous spinal cord stimulation prevents chloride homeostasis imbalance and the development of hyperreflexia after spinal cord injury in rat","volume":"376","author":"Malloy","year":"2024","journal-title":"Experimental Neurology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0430","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1007\/s00429-021-02315-7","article-title":"Transmitter and ion channel profiles of neurons in the primate abducens and trochlear nuclei","volume":"226","author":"Mayadali","year":"2021","journal-title":"Brain Structure and Function"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0435","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41401-023-01149-9","article-title":"Neuronal K(+)-Cl(-) cotransporter KCC2 as a promising drug target for epilepsy treatment","volume":"45","author":"McMoneagle","year":"2024","journal-title":"Acta Pharmacologica Sinica"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0440","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1113\/JP276952","article-title":"Repeated anodal trans-spinal direct current stimulation results in long-term reduction of spasticity in mice with spinal cord injury","volume":"597","author":"Mekhael","year":"2019","journal-title":"The Journal of Physiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0445","doi-asserted-by":"crossref","DOI":"10.3390\/ijms27167127","article-title":"Platelet-rich plasma modulates neuroinflammation in an iPSC model of sensory neurons and microglia","volume":"27","author":"Mercader-Ruiz","year":"2026","journal-title":"International Journal of Molecular Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0450","doi-asserted-by":"crossref","first-page":"10263","DOI":"10.1038\/s41598-019-46753-0","article-title":"Atrogin-1\/MAFbx mRNA expression is regulated by histone deacetylase 1 in rat soleus muscle under hindlimb unloading","volume":"9","author":"Mochalova","year":"2019","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0455","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.pain.2014.05.004","article-title":"Prevention of NKCC1 phosphorylation avoids downregulation of KCC2 in central sensory pathways and reduces neuropathic pain after peripheral nerve injury","volume":"155","author":"Modol","year":"2014","journal-title":"Pain"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0460","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fncel.2014.00007","article-title":"Differential effects on KCC2 expression and spasticity of ALS and traumatic injuries to motoneurons","volume":"8","author":"Modol","year":"2014","journal-title":"Frontiers in Cellular Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0465","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1073\/pnas.1810134115","article-title":"Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures","volume":"115","author":"Moore","year":"2018","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0470","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.bbrc.2007.05.133","article-title":"Essential role of NKCC1 in NGF-induced neurite outgrowth","volume":"359","author":"Nakajima","year":"2007","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0475","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000331723","article-title":"Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation of Na(+)\/K(+)\/2Cl(-) cotransporter","volume":"28","author":"Nakajima","year":"2011","journal-title":"Cellular Physiology and Biochemistry"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0480","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.brainresbull.2013.09.001","article-title":"Fatigue-induced motor cortex excitability changes in subjects with spinal cord injury","volume":"99","author":"Nardone","year":"2013","journal-title":"Brain Research Bulletin"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0485","first-page":"409","article-title":"Analgesic effect of bumetanide on neuropathic pain in patients with spinal cord injury","volume":"12","author":"Nasirinezhad","year":"2021","journal-title":"Basic Clinical Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0490","doi-asserted-by":"crossref","first-page":"346","DOI":"10.3389\/fnins.2019.00346","article-title":"Normalizing HDAC2 levels in the spinal cord alleviates thermal and mechanical hyperalgesia after peripheral nerve injury and promotes GAD65 and KCC2 expression","volume":"13","author":"Ouyang","year":"2019","journal-title":"Frontiers in Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0495","doi-asserted-by":"crossref","DOI":"10.1111\/cns.70045","article-title":"Combined use of CLP290 and bumetanide alleviates neuropathic pain and its mechanism after spinal cord injury in rats","volume":"30","author":"Pan","year":"2024","journal-title":"CNS Neuroscience & Therapeutics"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0500","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0166-2236(03)00068-7","article-title":"Cation-chloride co-transporters in neuronal communication, development and trauma","volume":"26","author":"Payne","year":"2003","journal-title":"Trends in Neurosciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0505","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1113\/jphysiol.2010.203703","article-title":"Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival","volume":"589","author":"Pellegrino","year":"2011","journal-title":"The Journal of Physiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0510","doi-asserted-by":"crossref","first-page":"6751","DOI":"10.1523\/JNEUROSCI.1337-07.2007","article-title":"NKCC1 phosphorylation stimulates neurite growth of injured adult sensory neurons","volume":"27","author":"Pieraut","year":"2007","journal-title":"Journal of Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0515","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aay0300","article-title":"Impaired regulation of KCC2 phosphorylation leads to neuronal network dysfunction and neurodevelopmental pathology","volume":"12","author":"Pisella","year":"2019","journal-title":"Science Signaling"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0520","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jpain.2012.10.003","article-title":"Stimulation of cutaneous low threshold mechanoreceptors in mice after intracolonic capsaicin increases spinal c-Fos labeling in an NKCC1-dependent fashion","volume":"14","author":"Pitcher","year":"2013","journal-title":"The Journal of Pain"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0525","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.pain.2010.09.008","article-title":"Role of the NKCC1 co-transporter in sensitization of spinal nociceptive neurons","volume":"151","author":"Pitcher","year":"2010","journal-title":"Pain"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0530","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.51404","article-title":"Calpain fosters the hyperexcitability of motoneurons after spinal cord injury and leads to spasticity","volume":"8","author":"Plantier","year":"2019","journal-title":"Elife"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0535","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/embr.201438749","article-title":"A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation","volume":"15","author":"Puskarjov","year":"2014","journal-title":"EMBO Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0540","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12974-025-03407-5","article-title":"Target inhibition of SPAK in choroid plexus attenuates T cell infiltration and demyelination in experimental autoimmune encephalomyelitis","volume":"22","author":"Qi","year":"2025","journal-title":"Journal of Neuroinflammation"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0545","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1374408","article-title":"Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases","volume":"15","author":"Rahman","year":"2024","journal-title":"Frontiers in Pharmacology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0550","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1083\/jcb.200209011","article-title":"BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion","volume":"159","author":"Rivera","year":"2002","journal-title":"Journal of Cell Biology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0555","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/13543784.2020.1813715","article-title":"New drugs on the horizon for cerebral edema: What\u2019s in the clinical development pipeline?","volume":"29","author":"Robert","year":"2020","journal-title":"Expert Opinion on Investigational Drugs"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0560","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.neuropharm.2017.02.006","article-title":"Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain","volume":"117","author":"R\u00f6mermann","year":"2017","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0565","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/cge.13049","article-title":"A de novo missense mutation in SLC12A5 found in a compound heterozygote patient with epilepsy of infancy with migrating focal seizures","volume":"92","author":"Saito","year":"2017","journal-title":"Clinical Genetics"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0570","doi-asserted-by":"crossref","first-page":"30072","DOI":"10.1038\/srep30072","article-title":"Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay","volume":"6","author":"Saitsu","year":"2016","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0575","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuroscience.2017.08.033","article-title":"Activation of 5-HT(2A) receptors restores KCC2 function and reduces neuropathic pain after spinal cord injury","volume":"387","author":"Sanchez-Brualla","year":"2018","journal-title":"Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0580","doi-asserted-by":"crossref","first-page":"8316","DOI":"10.3390\/ijms25158316","article-title":"Molecular signaling effects behind the spontaneous soleus muscle activity induced by 7-day rat hindlimb suspension","volume":"25","author":"Sergeeva","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0585","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.3390\/cimb45070354","article-title":"A prochlorperazine-induced decrease in autonomous muscle activity during hindlimb unloading is accompanied by preserved slow myosin mRNA expression","volume":"45","author":"Sharlo","year":"2023","journal-title":"Current Issues in Molecular Biology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0590","doi-asserted-by":"crossref","first-page":"12462","DOI":"10.3390\/ijms252212462","article-title":"Continuous use during disuse: mechanisms and effects of spontaneous activity of unloaded postural muscle","volume":"25","author":"Shenkman","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0595","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10974-025-09700-3","article-title":"The impact of mitokine MOTS-c administration on the soleus muscle of rats subjected to a 7-day hindlimb suspension","volume":"46","author":"Sidorenko","year":"2025","journal-title":"Journal of Muscle Research and Cell Motility"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0600","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13395-021-00285-2","article-title":"Novel gamma-sarcoglycan interactors in murine muscle membranes","volume":"12","author":"Smith","year":"2022","journal-title":"Skeletal Muscle"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0605","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1111\/j.1460-9568.2010.07592.x","article-title":"Contribution of the potassium-chloride co-transporter KCC2 to the modulation of lumbar spinal networks in mice","volume":"33","author":"Stil","year":"2011","journal-title":"European Journal of Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0610","doi-asserted-by":"crossref","DOI":"10.1212\/NXG.0000000000000478","article-title":"SLC12A2 mutations cause NKCC1 deficiency with encephalopathy and impaired secretory epithelia","volume":"6","author":"Stodberg","year":"2020","journal-title":"Neurology Genetics"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0615","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2022.1045520","article-title":"The role of KCC2 and NKCC1 in spinal cord injury: From physiology to pathology","volume":"13","author":"Talifu","year":"2022","journal-title":"Frontiers in Physiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0620","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2022.863793","article-title":"The overexpression of insulin-like growth factor-1 and neurotrophin-3 promote functional recovery and alleviate spasticity after spinal cord injury","volume":"16","author":"Talifu","year":"2022","journal-title":"Frontiers in Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0625","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1080\/09687688.2017.1393566","article-title":"K(+)-Cl(-) co-transporter 2 (KCC2) - a membrane trafficking perspective","volume":"33","author":"Tang","year":"2016","journal-title":"Molecular Membrane Biology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0630","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aau0164","article-title":"Pharmacological enhancement of KCC2 gene expression exerts therapeutic effects on human Rett syndrome neurons and Mecp2 mutant mice","volume":"11","author":"Tang","year":"2019","journal-title":"Science Translational Medicine"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0635","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1073\/pnas.1524013113","article-title":"KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome","volume":"113","author":"Tang","year":"2016","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0640","doi-asserted-by":"crossref","first-page":"9943","DOI":"10.1523\/JNEUROSCI.1989-09.2009","article-title":"The potassium chloride cotransporter KCC-2 coordinates development of inhibitory neurotransmission and synapse structure in Caenorhabditis elegans","volume":"29","author":"Tanis","year":"2009","journal-title":"Journal of Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0645","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1177\/1545968314562110","article-title":"BDNF induced by treadmill training contributes to the suppression of spasticity and allodynia after spinal cord injury via upregulation of KCC2","volume":"29","author":"Tashiro","year":"2015","journal-title":"Neurorehabilitation and Neural Repair"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0650","doi-asserted-by":"crossref","first-page":"9806","DOI":"10.1038\/s41598-021-89362-6","article-title":"Plantar mechanical stimulation attenuates protein synthesis decline in disused skeletal muscle via modulation of nitric oxide level","volume":"11","author":"Tyganov","year":"2021","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0655","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202100783R","article-title":"NOS-dependent effects of plantar mechanical stimulation on mechanical characteristics and cytoskeletal proteins in rat soleus muscle during hindlimb suspension","volume":"35","author":"Tyganov","year":"2021","journal-title":"The FASEB Journal"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0660","article-title":"Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library","volume":"17","author":"Uvarov","year":"2024","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0665","series-title":"Breathe, Walk and Chew: The Neural Challenge: Part II","first-page":"3","article-title":"Importance of chloride homeostasis in the operation of rhythmic motor networks","author":"Viemari","year":"2011"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0670","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.brainresrev.2007.09.003","article-title":"Plasticity of spinal cord locomotor networks and contribution of cation\u2013chloride cotransporters","volume":"57","author":"Vinay","year":"2008","journal-title":"Brain Research Reviews"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0675","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.bbrc.2020.08.082","article-title":"Coordinated downregulation of KCC2 and GABA(A) receptor contributes to inhibitory dysfunction during seizure induction","volume":"532","author":"Wan","year":"2020","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0680","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12974-022-02456-4","article-title":"Role of SPAK-NKCC1 signaling cascade in the choroid plexus blood-CSF barrier damage after stroke","volume":"19","author":"Wang","year":"2022","journal-title":"Journal of Neuroinflammation"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0685","article-title":"Functional recovery induced by KCC2-enabled relay pathways in completely injured spinal cords in adult rats","volume":"122","author":"Wang","year":"2025","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0690","doi-asserted-by":"crossref","first-page":"F353","DOI":"10.1152\/ajprenal.00271.2022","article-title":"Therapeutic effects of KCC2 chloride transporter activation on detrusor overactivity in mice with spinal cord injury","volume":"324","author":"Watanabe","year":"2023","journal-title":"American Journal of Physiology. Renal Physiology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0695","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/nchembio.2168","article-title":"Small-molecule WNK inhibition regulates cardiovascular and renal function","volume":"12","author":"Yamada","year":"2016","journal-title":"Nature Chemical Biology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0700","doi-asserted-by":"crossref","first-page":"6208","DOI":"10.1038\/s41467-021-26270-3","article-title":"Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission","volume":"12","author":"Yeo","year":"2021","journal-title":"Nature Communications"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0705","doi-asserted-by":"crossref","DOI":"10.1088\/1748-605X\/ac956b","article-title":"KCC2 overexpressed exosomes meditated spinal cord injury recovery in mice","volume":"17","author":"Yin","year":"2022","journal-title":"Biomedical Materials"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0710","doi-asserted-by":"crossref","first-page":"13630","DOI":"10.1523\/JNEUROSCI.2864-12.2012","article-title":"NKCC1 knockdown decreases neuron production through GABA(A)-regulated neural progenitor proliferation and delays dendrite development","volume":"32","author":"Young","year":"2012","journal-title":"Journal of Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0715","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.jocn.2020.10.010","article-title":"Preliminary study of analgesic effect of bumetanide on neuropathic pain in patients with spinal cord injury","volume":"81","author":"Zarepour","year":"2020","journal-title":"Journal of Clinical Neuroscience"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0720","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/s42003-025-08734-0","article-title":"AAV9-mediated KCC2 upregulation enhances functional recovery following cervical spinal cord injury","volume":"8","author":"Zavvarian","year":"2025","journal-title":"Communications Biology"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0725","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41467-019-13851-6","article-title":"Modulation of brain cation-Cl(-) cotransport via the SPAK kinase inhibitor ZT-1a","volume":"11","author":"Zhang","year":"2020","journal-title":"Nature Communications"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0730","doi-asserted-by":"crossref","DOI":"10.1016\/j.mtbio.2025.102624","article-title":"Functionalized nanozyme delivery of a KCC2-activator conjugate for the promotion of functional recovery after acute spinal cord injury","volume":"35","author":"Zhao","year":"2025","journal-title":"Materials Today Bio"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0735","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1177\/0271678X16631561","article-title":"Deletion of the WNK3-SPAK kinase complex in mice improves radiographic and clinical outcomes in malignant cerebral edema after ischemic stroke","volume":"37","author":"Zhao","year":"2017","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"10.1016\/j.pharmthera.2026.109129_bb0740","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.2464","article-title":"Involvement of the BDNF-TrkB-KCC2 pathway in neuropathic pain after brachial plexus avulsion","volume":"12","author":"Zhao","year":"2022","journal-title":"Brain and Behavior"}],"container-title":["Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725826001567?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725826001567?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T16:02:36Z","timestamp":1794412956000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0163725826001567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":148,"alternative-id":["S0163725826001567"],"URL":"https:\/\/doi.org\/10.1016\/j.pharmthera.2026.109129","relation":{},"ISSN":["0163-7258"],"issn-type":[{"value":"0163-7258","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting KCC2 and NKCC1 for spinal motor dysfunction: pharmacology, therapeutic opportunities, and translational roadmap","name":"articletitle","label":"Article Title"},{"value":"Pharmacology & Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pharmthera.2026.109129","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"109129"}}