{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:55:16Z","timestamp":1791312916568,"version":"4.3.1"},"reference-count":96,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-08734-0","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:37:47Z","timestamp":1761050267000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AAV9-mediated KCC2 upregulation enhances functional recovery following cervical spinal cord injury"],"prefix":"10.1038","volume":"8","author":[{"given":"Mohammad-Masoud","family":"Zavvarian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-3670","authenticated-orcid":false,"given":"Akshat D.","family":"Modi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Khazaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Velumian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar Imad","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Ahuja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeenal H.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6080-6880","authenticated-orcid":false,"given":"Zhigang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5722-6364","authenticated-orcid":false,"given":"Michael G.","family":"Fehlings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"8734_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.18","volume":"3","author":"CS Ahuja","year":"2017","unstructured":"Ahuja, C. S. et al. Traumatic spinal cord injury. Nat. Rev. Dis. Prim. 3, 17018 (2017).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"8734_CR2","unstructured":"World Health Organization. Spinal cord injury. www.who.int\/news-room\/fact-sheets\/detail\/spinal-cord-injury (2024)."},{"key":"8734_CR3","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s41582-019-0280-3","volume":"15","author":"TH Hutson","year":"2019","unstructured":"Hutson, T. H. & Di Giovanni, S. The translational landscape in spinal cord injury: focus on neuroplasticity and regeneration. Nat. Rev. Neurol. 15, 732\u2013745 (2019).","journal-title":"Nat. Rev. Neurol."},{"key":"8734_CR4","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/sj.sc.3102007","volume":"45","author":"JW Fawcett","year":"2007","unstructured":"Fawcett, J. W. et al. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord. 45, 190\u2013205 (2007).","journal-title":"Spinal Cord."},{"key":"8734_CR5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41582-020-00436-x","volume":"17","author":"K Fouad","year":"2021","unstructured":"Fouad, K., Popovich, P. G., Kopp, M. A. & Schwab, J. M. The neuroanatomical\u2013functional paradox in spinal cord injury. Nat. Rev. Neurol. 17, 53\u201362 (2021).","journal-title":"Nat. Rev. Neurol."},{"key":"8734_CR6","doi-asserted-by":"crossref","unstructured":"Ditunno, J., Little, J., Tessler, A. & Burns, A. Spinal shock revisited: a four-phase model. Spinal Cord 42, 383-95 (2004).","DOI":"10.1038\/sj.sc.3101603"},{"key":"8734_CR7","doi-asserted-by":"publisher","DOI":"10.1177\/17562864211070657","volume":"15","author":"A Stampas","year":"2022","unstructured":"Stampas, A. et al. Evidence of treating spasticity before it develops: a systematic review of spasticity outcomes in acute spinal cord injury interventional trials. Ther. Adv. Neurol. Disord. 15, 17562864211070657 (2022).","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"8734_CR8","doi-asserted-by":"publisher","unstructured":"Singh, A., Tetreault, L., Kalsi-Ryan, S., Nouri, A. & Michael, F. Global prevalence and incidence of traumatic spinal cord injury. CLEP https:\/\/doi.org\/10.2147\/CLEP.S68889 (2014).","DOI":"10.2147\/CLEP.S68889"},{"key":"8734_CR9","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1089\/neu.2014.3718","volume":"32","author":"EJ Gonzalez-Rothi","year":"2015","unstructured":"Gonzalez-Rothi, E. J. et al. Spinal interneurons and forelimb plasticity after incomplete cervical spinal cord injury in adult rats. J. Neurotrauma 32, 893\u2013907 (2015).","journal-title":"J. Neurotrauma"},{"key":"8734_CR10","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0168-5597(93)90131-8","volume":"89","author":"B Calancie","year":"1993","unstructured":"Calancie, B. et al. Evidence that alterations in presynaptic inhibition contribute to segmental hypo- and hyperexcitability after spinal cord injury in man. Electroencephalogr. Clin. Neurophysiol. Evoked Potentials Sect. 89, 177\u2013186 (1993).","journal-title":"Electroencephalogr. Clin. Neurophysiol. Evoked Potentials Sect."},{"key":"8734_CR11","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.1172\/JCI90608","volume":"127","author":"TM O\u2019Shea","year":"2017","unstructured":"O\u2019Shea, T. M., Burda, J. E. & Sofroniew, M. V. Cell biology of spinal cord injury and repair. J. Clin. Investig. 127, 3259\u20133270 (2017).","journal-title":"J. Clin. Investig."},{"key":"8734_CR12","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1002\/acn3.679","volume":"6","author":"CR Jutzeler","year":"2019","unstructured":"Jutzeler, C. R. et al. Sensorimotor plasticity after spinal cord injury: a longitudinal and translational study. Ann. Clin. Transl. Neurol. 6, 68\u201382 (2019).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"8734_CR13","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1212\/WNL.42.3.623","volume":"42","author":"ML Aisen","year":"1992","unstructured":"Aisen, M. L., Brown, W. & Rubin, M. Electrophysiologic changes in lumbar spinal cord after cervical cord injury. Neurology 42, 623\u2013623 (1992).","journal-title":"Neurology"},{"key":"8734_CR14","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.brainresrev.2007.09.002","volume":"57","author":"VR Edgerton","year":"2008","unstructured":"Edgerton, V. R. et al. Training locomotor networks. Brain Res. Rev. 57, 241\u2013254 (2008).","journal-title":"Brain Res. Rev."},{"key":"8734_CR15","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1146\/annurev-neuro-061010-113746","volume":"34","author":"S Rossignol","year":"2011","unstructured":"Rossignol, S. & Frigon, A. Recovery of locomotion after spinal cord injury: some facts and mechanisms. Annu. Rev. Neurosci. 34, 413\u2013440 (2011).","journal-title":"Annu. Rev. Neurosci."},{"key":"8734_CR16","doi-asserted-by":"crossref","unstructured":"Chamma, I., Chevy, Q., Poncer, J. C. & L\u00e9vi, S. Role of the neuronal K-Cl co-transporter KCC2 in inhibitory and excitatory neurotransmission. Front. Cell. Neurosci. 6, 1-15 (2012).","DOI":"10.3389\/fncel.2012.00005"},{"key":"8734_CR17","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nm.2107","volume":"16","author":"P Boulenguez","year":"2010","unstructured":"Boulenguez, P. et al. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat. Med. 16, 302\u2013307 (2010).","journal-title":"Nat. Med."},{"key":"8734_CR18","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3389\/fncel.2020.00127","volume":"14","author":"M-M Zavvarian","year":"2020","unstructured":"Zavvarian, M.-M., Hong, J. & Fehlings, M. G. The functional role of spinal interneurons following traumatic spinal cord injury. Front. Cell. Neurosci. 14, 127 (2020).","journal-title":"Front. Cell. Neurosci."},{"key":"8734_CR19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nm1682","volume":"14","author":"G Courtine","year":"2008","unstructured":"Courtine, G. et al. Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat. Med. 14, 69\u201374 (2008).","journal-title":"Nat. Med."},{"key":"8734_CR20","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1126\/science.1217416","volume":"336","author":"Brand","year":"2012","unstructured":"Brand et al. Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science 336, 1182\u20131185 (2012).","journal-title":"Science"},{"key":"8734_CR21","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.cell.2018.06.005","volume":"174","author":"B Chen","year":"2018","unstructured":"Chen, B. et al. Reactivation of dormant relay pathways in injured spinal cord by KCC2 manipulations. Cell 174, 521\u2013535.e13 (2018).","journal-title":"Cell"},{"key":"8734_CR22","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1038\/nm.3356","volume":"19","author":"M Gagnon","year":"2013","unstructured":"Gagnon, M. et al. Chloride extrusion enhancers as novel therapeutics for neurological diseases. Nat. Med. 19, 1524\u20131528 (2013).","journal-title":"Nat. Med."},{"key":"8734_CR23","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1056\/NEJMra1706910","volume":"381","author":"KA High","year":"2019","unstructured":"High, K. A. & Roncarolo, M. G. Gene therapy. N. Engl. J. Med. 381, 455\u2013464 (2019).","journal-title":"N. Engl. J. Med."},{"key":"8734_CR24","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4672","volume":"359","author":"CE Dunbar","year":"2018","unstructured":"Dunbar, C. E. et al. Gene therapy comes of age. Science 359, eaan4672 (2018).","journal-title":"Science"},{"key":"8734_CR25","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.ymthe.2018.01.018","volume":"26","author":"J Hordeaux","year":"2018","unstructured":"Hordeaux, J. et al. The neurotropic properties of AAV-PHP.B are limited to C57BL\/6J mice. Mol. Ther. 26, 664\u2013668 (2018).","journal-title":"Mol. Ther."},{"key":"8734_CR26","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s11689-018-9234-0","volume":"10","author":"EA Lykken","year":"2018","unstructured":"Lykken, E. A., Shyng, C., Edwards, R. J., Rozenberg, A. & Gray, S. J. Recent progress and considerations for AAV gene therapies targeting the central nervous system. J. Neurodev. Disord. 10, 16 (2018).","journal-title":"J. Neurodev. Disord."},{"key":"8734_CR27","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1021\/acssynbio.2c00589","volume":"12","author":"LT Collins","year":"2023","unstructured":"Collins, L. T., Ponnazhagan, S. & Curiel, D. T. Synthetic biology design as a paradigm shift toward manufacturing affordable adeno-associated virus gene therapies. ACS Synth. Biol. 12, 17\u201326 (2023).","journal-title":"ACS Synth. Biol."},{"key":"8734_CR28","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/sj.gt.3301905","volume":"10","author":"S K\u00fcgler","year":"2003","unstructured":"K\u00fcgler, S., Kilic, E. & B\u00e4hr, M. Human synapsin 1 gene promoter confers highly neuron-specific long-term transgene expression from an adenoviral vector in the adult rat brain depending on the transduced area. Gene Ther. 10, 337\u2013347 (2003).","journal-title":"Gene Ther."},{"key":"8734_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14154-6","volume":"11","author":"L-E Lorenzo","year":"2020","unstructured":"Lorenzo, L.-E. et al. Enhancing neuronal chloride extrusion rescues \u03b12\/\u03b13 GABAA-mediated analgesia in neuropathic pain. Nat. Commun. 11, 869 (2020).","journal-title":"Nat. Commun."},{"key":"8734_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynpai.2023.100115","volume":"13","author":"M Shi","year":"2023","unstructured":"Shi, M. et al. EA participates in pain transition through regulating KCC2 expression by BDNF-TrkB in the spinal cord dorsal horn of male rats. Neurobiol. Pain. 13, 100115 (2023).","journal-title":"Neurobiol. Pain."},{"key":"8734_CR31","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.celrep.2019.06.059","volume":"28","author":"JCS Mapplebeck","year":"2019","unstructured":"Mapplebeck, J. C. S. et al. Chloride dysregulation through downregulation of KCC2 mediates neuropathic pain in both sexes. Cell Rep. 28, 590\u2013596.e4 (2019).","journal-title":"Cell Rep."},{"key":"8734_CR32","doi-asserted-by":"crossref","unstructured":"Tavazzani, E. et al. Glutamic acid decarboxylase 67 expression by a distinct population of mouse vestibular supporting cells. Front. Cell. Neurosci. 8, 1-9 (2014).","DOI":"10.3389\/fncel.2014.00428"},{"key":"8734_CR33","doi-asserted-by":"publisher","first-page":"9733","DOI":"10.1523\/JNEUROSCI.18-23-09733.1998","volume":"18","author":"FA Chaudhry","year":"1998","unstructured":"Chaudhry, F. A. et al. The vesicular GABA transporter, VGAT, localizes to synaptic vesicles in sets of glycinergic as well as GABAergic neurons. J. Neurosci. 18, 9733\u20139750 (1998).","journal-title":"J. Neurosci."},{"key":"8734_CR34","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1111\/jnc.12393","volume":"127","author":"N Juge","year":"2013","unstructured":"Juge, N., Omote, H. & Moriyama, Y. Vesicular GABA transporter (VGAT) transports \u03b2-alanine. J. Neurochem. 127, 482\u2013486 (2013).","journal-title":"J. Neurochem."},{"key":"8734_CR35","doi-asserted-by":"publisher","first-page":"113605","DOI":"10.1016\/j.expneurol.2021.113605","volume":"338","author":"JN Bilchak","year":"2021","unstructured":"Bilchak, J. N., Yeakle, K., Caron, G., Malloy, D. & C\u00f4t\u00e9, M.-P. Enhancing KCC2 activity decreases hyperreflexia and spasticity after chronic spinal cord injury. Exp. Neurol. 338, 113605 (2021).","journal-title":"Exp. Neurol."},{"key":"8734_CR36","unstructured":"National Spinal Cord Injury Statistical Center. Traumatic Spinal Cord Injury Facts and Figures at a Glance (University of Alabama at Birmingham, 2023)."},{"key":"8734_CR37","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.3390\/ijms19082167","volume":"19","author":"J Hong","year":"2018","unstructured":"Hong, J. et al. Level-specific differences in systemic expression of pro- and anti-inflammatory cytokines and chemokines after spinal cord injury. Int. J. Mol. Sci. 19, 2167 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"8734_CR38","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/sj.sc.3101597","volume":"42","author":"M Adams","year":"2004","unstructured":"Adams, M. & Cavanagh, J. F. R. International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP): another step forward for spinal cord injury research. Spinal Cord 42, 273\u2013280 (2004).","journal-title":"Spinal Cord"},{"key":"8734_CR39","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/sj.sc.3102009","volume":"45","author":"MH Tuszynski","year":"2007","unstructured":"Tuszynski, M. H. et al. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion\/exclusion criteria and ethics. Spinal Cord. 45, 222\u2013231 (2007).","journal-title":"Spinal Cord."},{"key":"8734_CR40","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/sj.sc.3102008","volume":"45","author":"JD Steeves","year":"2007","unstructured":"Steeves, J. D. et al. Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. Spinal Cord. 45, 206\u2013221 (2007).","journal-title":"Spinal Cord."},{"key":"8734_CR41","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/s41591-019-0475-6","volume":"25","author":"G Courtine","year":"2019","unstructured":"Courtine, G. & Sofroniew, M. V. Spinal cord repair: advances in biology and technology. Nat. Med. 25, 898\u2013908 (2019).","journal-title":"Nat. Med."},{"key":"8734_CR42","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/0013-4694(88)90036-3","volume":"69","author":"MG Fehlings","year":"1988","unstructured":"Fehlings, M. G., Tator, C. H., Linden, R. D. & Piper, I. R. Motor and somatosensory evoked potentials recorded from the rat. Electroencephalogr. Clin. Neurophysiol. 69, 65\u201378 (1988).","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"8734_CR43","doi-asserted-by":"crossref","unstructured":"Fehlings, M. G., Tator, C. H. & Linden, R. D. The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. Electroencephalogr. Clin. Neurophysiol. 74, 241\u2013259 (1989).","DOI":"10.1016\/0168-5597(89)90055-5"},{"key":"8734_CR44","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.expneurol.2009.08.020","volume":"220","author":"KD Anderson","year":"2009","unstructured":"Anderson, K. D. et al. Forelimb locomotor assessment scale (FLAS): novel assessment of forelimb dysfunction after cervical spinal cord injury. Exp. Neurol. 220, 23\u201333 (2009).","journal-title":"Exp. Neurol."},{"key":"8734_CR45","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.expneurol.2007.05.024","volume":"206","author":"KD Anderson","year":"2007","unstructured":"Anderson, K. D., Gunawan, A. & Steward, O. Spinal pathways involved in the control of forelimb motor function in rats. Exp. Neurol. 206, 318\u2013331 (2007).","journal-title":"Exp. Neurol."},{"key":"8734_CR46","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1089\/neu.2006.23.537","volume":"23","author":"FPT Hamers","year":"2006","unstructured":"Hamers, F. P. T., Koopmans, G. C. & Joosten, E. A. J. CatWalk-assisted gait analysis in the assessment of spinal cord injury. J. Neurotrauma 23, 537\u2013548 (2006).","journal-title":"J. Neurotrauma"},{"key":"8734_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/neu.1995.12.1","volume":"12","author":"DM Basso","year":"1995","unstructured":"Basso, D. M., Beattie, M. S. & Bresnahan, J. C. A sensitive and reliable locomotor rating scale for open field testing in rats. J. Neurotrauma 12, 1\u201321 (1995).","journal-title":"J. Neurotrauma"},{"key":"8734_CR48","doi-asserted-by":"publisher","first-page":"577","DOI":"10.3171\/jns.1977.47.4.0577","volume":"47","author":"AS Rivlin","year":"1977","unstructured":"Rivlin, A. S. & Tator, C. H. Objective clinical assessment of motor function after experimental spinal cord injury in the rat. J. Neurosurg. 47, 577\u2013581 (1977).","journal-title":"J. Neurosurg."},{"key":"8734_CR49","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nn.2448","volume":"13","author":"A Ghosh","year":"2010","unstructured":"Ghosh, A. et al. Rewiring of hindlimb corticospinal neurons after spinal cord injury. Nat. Neurosci. 13, 97\u2013104 (2010).","journal-title":"Nat. Neurosci."},{"key":"8734_CR50","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1093\/brain\/aws115","volume":"135","author":"B Zaaimi","year":"2012","unstructured":"Zaaimi, B., Edgley, S. A., Soteropoulos, D. S. & Baker, S. N. Changes in descending motor pathway connectivity after corticospinal tract lesion in macaque monkey. Brain 135, 2277\u20132289 (2012).","journal-title":"Brain"},{"key":"8734_CR51","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.expneurol.2013.05.003","volume":"247","author":"N Weishaupt","year":"2013","unstructured":"Weishaupt, N., Hurd, C., Wei, D. Z. & Fouad, K. Reticulospinal plasticity after cervical spinal cord injury in the rat involves withdrawal of projections below the injury. Exp. Neurol. 247, 241\u2013249 (2013).","journal-title":"Exp. Neurol."},{"key":"8734_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113543","volume":"339","author":"KK Fenrich","year":"2021","unstructured":"Fenrich, K. K. et al. Self-directed rehabilitation training intensity thresholds for efficient recovery of skilled forelimb function in rats with cervical spinal cord injury. Exp. Neurol. 339, 113543 (2021).","journal-title":"Exp. Neurol."},{"key":"8734_CR53","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1016\/j.celrep.2018.01.007","volume":"22","author":"R Priya","year":"2018","unstructured":"Priya, R. et al. Activity regulates cell death within cortical interneurons through a calcineurin-dependent mechanism. Cell Rep. 22, 1695\u20131709 (2018).","journal-title":"Cell Rep."},{"key":"8734_CR54","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41586-018-0139-6","volume":"557","author":"FK Wong","year":"2018","unstructured":"Wong, F. K. et al. Pyramidal cell regulation of interneuron survival sculpts cortical networks. Nature 557, 668\u2013673 (2018).","journal-title":"Nature"},{"key":"8734_CR55","doi-asserted-by":"publisher","first-page":"eadn7095","DOI":"10.1126\/scitranslmed.adn7095","volume":"16","author":"Q Li","year":"2024","unstructured":"Li, Q. et al. Reduction of prolonged excitatory neuron swelling after spinal cord injury improves locomotor recovery in mice. Sci. Transl. Med. 16, eadn7095 (2024).","journal-title":"Sci. Transl. Med."},{"key":"8734_CR56","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1007\/s00424-003-1066-3","volume":"447","author":"SC Hebert","year":"2004","unstructured":"Hebert, S. C., Mount, D. B. & Gamba, G. Molecular physiology of cation-coupled Cl? cotransport: the SLC12 family. Pflug. Arch. Eur. J. Physiol. 447, 580\u2013593 (2004).","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"8734_CR57","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jneuroim.2004.01.011","volume":"150","author":"R Vlkolinsk\u00fd","year":"2004","unstructured":"Vlkolinsk\u00fd, R., Siggins, G. R., Campbell, I. L. & Krucker, T. Acute exposure to CXC chemokine ligand 10, but not its chronic astroglial production, alters synaptic plasticity in mouse hippocampal slices. J. Neuroimmunol. 150, 37\u201347 (2004).","journal-title":"J. Neuroimmunol."},{"key":"8734_CR58","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1177\/1721727X1201000307","volume":"10","author":"JN Kodangattil","year":"2012","unstructured":"Kodangattil, J. N., M\u00f6ddel, G., M\u00fcller, M., Weber, W. & Gorji, A. The inflammatory chemokine CXCL10 modulates synaptic plasticity and neuronal activity in the hippocampus. Eur. J. Inflamm. 10, 311\u2013328 (2012).","journal-title":"Eur. J. Inflamm."},{"key":"8734_CR59","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1006\/bbrc.2001.5388","volume":"286","author":"Y Sasaki","year":"2001","unstructured":"Sasaki, Y., Ohsawa, K., Kanazawa, H., Kohsaka, S. & Imai, Y. Iba1 is an actin-cross-linking protein in macrophages\/microglia. Biochem. Biophys. Res. Commun. 286, 292\u2013297 (2001).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"8734_CR60","doi-asserted-by":"publisher","unstructured":"Bilchak, J. N., Caron, G., Danner, S. M. & C\u00f4t\u00e9, M.-P. KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2023.10.21.563363 (2023).","DOI":"10.1101\/2023.10.21.563363"},{"key":"8734_CR61","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1089\/neu.2019.6526","volume":"37","author":"H Beverungen","year":"2020","unstructured":"Beverungen, H., Klaszky, S. C., Klaszky, M. & C\u00f4t\u00e9, M.-P. Rehabilitation decreases spasticity by restoring chloride homeostasis through the brain-derived neurotrophic factor\u2013KCC2 pathway after spinal cord injury. J. Neurotrauma 37, 846\u2013859 (2020).","journal-title":"J. Neurotrauma"},{"key":"8734_CR62","doi-asserted-by":"publisher","unstructured":"Detloff, M. R., Fisher, L. C., Deibert, R. J. & Basso, D. M. Acute and chronic tactile sensory testing after spinal cord injury in rats. J. Vis. Exp. https:\/\/doi.org\/10.3791\/3247 (2012).","DOI":"10.3791\/3247"},{"key":"8734_CR63","doi-asserted-by":"publisher","first-page":"275","DOI":"10.13004\/kjnt.2023.19.e43","volume":"19","author":"JH Kang","year":"2023","unstructured":"Kang, J. H. & Im, S. Functional anatomy of the spinal tracts based on evolutionary perspectives. Korean J. Neurotrauma 19, 275 (2023).","journal-title":"Korean J. Neurotrauma"},{"key":"8734_CR64","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1182\/blood-2013-01-306647","volume":"122","author":"F Mingozzi","year":"2013","unstructured":"Mingozzi, F. & High, K. A. Immune responses to AAV vectors: Overcoming barriers to successful gene therapy. Blood 122, 23\u201336 (2013).","journal-title":"Blood"},{"key":"8734_CR65","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/s41583-020-00382-z","volume":"21","author":"AR Nectow","year":"2020","unstructured":"Nectow, A. R. & Nestler, E. J. Viral tools for neuroscience. Nat. Rev. Neurosci. 21, 669\u2013681 (2020).","journal-title":"Nat. Rev. Neurosci."},{"key":"8734_CR66","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","volume":"18","author":"D Wang","year":"2019","unstructured":"Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358\u2013378 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"8734_CR67","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1038\/nn.4593","volume":"20","author":"KY Chan","year":"2017","unstructured":"Chan, K. Y. et al. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat. Neurosci. 20, 1172\u20131179 (2017).","journal-title":"Nat. Neurosci."},{"key":"8734_CR68","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/14712598.2018.1416089","volume":"18","author":"N Hardcastle","year":"2018","unstructured":"Hardcastle, N., Boulis, N. M. & Federici, T. AAV gene delivery to the spinal cord: serotypes, methods, candidate diseases, and clinical trials. Expert Opin. Biol. Ther. 18, 293\u2013307 (2018).","journal-title":"Expert Opin. Biol. Ther."},{"key":"8734_CR69","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1016\/j.neuron.2022.05.003","volume":"110","author":"X Chen","year":"2022","unstructured":"Chen, X. et al. Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems. Neuron 110, 2242\u20132257.e6 (2022).","journal-title":"Neuron"},{"key":"8734_CR70","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/s41593-021-00969-4","volume":"25","author":"D Goertsen","year":"2022","unstructured":"Goertsen, D. et al. AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset. Nat. Neurosci. 25, 106\u2013115 (2022).","journal-title":"Nat. Neurosci."},{"key":"8734_CR71","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-20980-4","volume":"12","author":"B Brommer","year":"2021","unstructured":"Brommer, B. et al. Improving hindlimb locomotor function by non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury. Nat. Commun. 12, 781 (2021).","journal-title":"Nat. Commun."},{"key":"8734_CR72","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1089\/hum.2020.167","volume":"31","author":"J Hordeaux","year":"2020","unstructured":"Hordeaux, J. et al. Adeno-associated virus-induced dorsal root ganglion pathology. Hum. Gene Ther. 31, 808\u2013818 (2020).","journal-title":"Hum. Gene Ther."},{"key":"8734_CR73","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41591-019-0674-1","volume":"26","author":"M Bravo-Hernandez","year":"2020","unstructured":"Bravo-Hernandez, M. et al. Spinal subpial delivery of AAV9 enables widespread gene silencing and blocks motoneuron degeneration in ALS. Nat. Med 26, 118\u2013130 (2020).","journal-title":"Nat. Med"},{"key":"8734_CR74","unstructured":"Hong, J. Y.-L. A Comparison between Cervical and Thoracic Spinal Cord Injury: Critical Level-Dependent Differences in Pathobiology (University of Toronto, 2020)."},{"key":"8734_CR75","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1080\/14728222.2020.1762174","volume":"24","author":"PQ Duy","year":"2020","unstructured":"Duy, P. Q., He, M., He, Z. & Kahle, K. T. Preclinical insights into therapeutic targeting of KCC2 for disorders of neuronal hyperexcitability. Expert Opin. Ther. Targets 24, 629\u2013637 (2020).","journal-title":"Expert Opin. Ther. Targets"},{"key":"8734_CR76","doi-asserted-by":"publisher","first-page":"eaau0164","DOI":"10.1126\/scitranslmed.aau0164","volume":"11","author":"X Tang","year":"2019","unstructured":"Tang, X. et al. Pharmacological enhancement of KCC2 gene expression exerts therapeutic effects on human Rett syndrome neurons and Mecp2 mutant mice. Sci. Transl. Med. 11, eaau0164 (2019).","journal-title":"Sci. Transl. Med."},{"key":"8734_CR77","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26270-3","volume":"12","author":"M Yeo","year":"2021","unstructured":"Yeo, M. et al. Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission. Nat. Commun. 12, 6208 (2021).","journal-title":"Nat. Commun."},{"key":"8734_CR78","doi-asserted-by":"crossref","unstructured":"Phukan, S., Babu, V., Kannoji, A., Hariharan, R. & Balaji, V. GSK3b: role in therapeutic landscape and development of modulators. Br. J. Pharmacol. 160, 1\u20139 (2010).","DOI":"10.1111\/j.1476-5381.2010.00661.x"},{"key":"8734_CR79","doi-asserted-by":"publisher","first-page":"1045520","DOI":"10.3389\/fphys.2022.1045520","volume":"13","author":"Z Talifu","year":"2022","unstructured":"Talifu, Z. et al. The role of KCC2 and NKCC1 in spinal cord injury: From physiology to pathology. Front. Physiol. 13, 1045520 (2022).","journal-title":"Front. Physiol."},{"key":"8734_CR80","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1177\/1545968305274517","volume":"19","author":"KS Beekhuizen","year":"2005","unstructured":"Beekhuizen, K. S. & Field-Fote, E. C. Massed practice versus massed practice with stimulation: effects on upper extremity function and cortical plasticity in individuals with incomplete cervical spinal cord injury. Neurorehabil. Neural Repair 19, 33\u201345 (2005).","journal-title":"Neurorehabil. Neural Repair"},{"key":"8734_CR81","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1177\/107385840100700514","volume":"7","author":"SJ Harkema","year":"2001","unstructured":"Harkema, S. J. Neural plasticity after human spinal cord injury: application of locomotor training to the rehabilitation of walking. Neuroscientist 7, 455\u2013468 (2001).","journal-title":"Neuroscientist"},{"key":"8734_CR82","doi-asserted-by":"crossref","unstructured":"Hicks, A. et al. Long-term body-weight-supported treadmill training and subsequent follow-up in persons with chronic SCI: effects on functional walking ability and measures of subjective well-being. Spinal Cord 43, 291-298 (2005).","DOI":"10.1038\/sj.sc.3101710"},{"key":"8734_CR83","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1177\/1545968310394869","volume":"25","author":"J Kowalczewski","year":"2011","unstructured":"Kowalczewski, J., Chong, S. L., Galea, M. & Prochazka, A. In-home tele-rehabilitation improves tetraplegic hand function. Neurorehabil. Neural Repair 25, 412\u2013422 (2011).","journal-title":"Neurorehabil. Neural Repair"},{"key":"8734_CR84","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1177\/1545968314562110","volume":"29","author":"S Tashiro","year":"2015","unstructured":"Tashiro, S. et al. BDNF induced by treadmill training contributes to the suppression of spasticity and allodynia after spinal cord injury via upregulation of KCC2. Neurorehabil. Neural Repair 29, 677\u2013689 (2015).","journal-title":"Neurorehabil. Neural Repair"},{"key":"8734_CR85","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/0006-8993(87)91442-9","volume":"412","author":"H Barbeau","year":"1987","unstructured":"Barbeau, H. & Rossignol, S. Recovery of locomotion after chronic spinalization in the adult cat. Brain Res. 412, 84\u201395 (1987).","journal-title":"Brain Res."},{"key":"8734_CR86","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1089\/neu.2011.2199","volume":"29","author":"CR Battistuzzo","year":"2012","unstructured":"Battistuzzo, C. R., Callister, R. J., Callister, R. & Galea, M. P. A systematic review of exercise training to promote locomotor recovery in animal models of spinal cord injury. J. Neurotrauma 29, 1600\u20131613 (2012).","journal-title":"J. Neurotrauma"},{"key":"8734_CR87","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/nn.2377","volume":"12","author":"G Garc\u00eda-Al\u00edas","year":"2009","unstructured":"Garc\u00eda-Al\u00edas, G., Barkhuysen, S., Buckle, M. & Fawcett, J. W. Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat. Neurosci. 12, 1145\u20131151 (2009).","journal-title":"Nat. Neurosci."},{"key":"8734_CR88","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1177\/1545968314520721","volume":"28","author":"ML Starkey","year":"2014","unstructured":"Starkey, M. L. et al. High-impact, self-motivated training within an enriched environment with single animal tracking dose-dependently promotes motor skill acquisition and functional recovery. Neurorehabil. Neural Repair 28, 594\u2013605 (2014).","journal-title":"Neurorehabil. Neural Repair"},{"key":"8734_CR89","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1089\/neu.2018.5906","volume":"35","author":"A Torres-Esp\u00edn","year":"2018","unstructured":"Torres-Esp\u00edn, A., Beaudry, E., Fenrich, K. & Fouad, K. Rehabilitative training in animal models of spinal cord injury. J. Neurotrauma 35, 1970\u20131985 (2018).","journal-title":"J. Neurotrauma"},{"key":"8734_CR90","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1093\/brain\/awy128","volume":"141","author":"A Torres-Esp\u00edn","year":"2018","unstructured":"Torres-Esp\u00edn, A. et al. Eliciting inflammation enables successful rehabilitative training in chronic spinal cord injury. Brain 141, 1946\u20131962 (2018).","journal-title":"Brain"},{"key":"8734_CR91","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/jcm4010037","volume":"4","author":"M Khazaei","year":"2014","unstructured":"Khazaei, M., Siddiqui, A. & Fehlings, M. The potential for iPS-derived stem cells as a therapeutic strategy for spinal cord injury: opportunities and challenges. J. Clin. Med. 4, 37\u201365 (2014).","journal-title":"J. Clin. Med."},{"key":"8734_CR92","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41583-020-0314-2","volume":"21","author":"I Fischer","year":"2020","unstructured":"Fischer, I., Dulin, J. N. & Lane, M. A. Transplanting neural progenitor cells to restore connectivity after spinal cord injury. Nat. Rev. Neurosci. 21, 366\u2013383 (2020).","journal-title":"Nat. Rev. Neurosci."},{"key":"8734_CR93","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.nbd.2017.05.009","volume":"105","author":"JT Wilcox","year":"2017","unstructured":"Wilcox, J. T. et al. Generating level-dependent models of cervical and thoracic spinal cord injury: exploring the interplay of neuroanatomy, physiology, and function. Neurobiol. Dis. 105, 194\u2013212 (2017).","journal-title":"Neurobiol. Dis."},{"key":"8734_CR94","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.omtm.2018.06.003","volume":"10","author":"J Hordeaux","year":"2018","unstructured":"Hordeaux, J. et al. Toxicology study of intra-cisterna magna adeno-associated virus 9 expressing human alpha-L-iduronidase in rhesus macaques. Mol. Ther. Methods Clin. Dev. 10, 79\u201388 (2018).","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"8734_CR95","doi-asserted-by":"publisher","first-page":"972","DOI":"10.3390\/biom11070972","volume":"11","author":"M-M Zavvarian","year":"2021","unstructured":"Zavvarian, M.-M. et al. The protein kinase inhibitor midostaurin improves functional neurological recovery and attenuates inflammatory changes following traumatic cervical spinal cord injury. Biomolecules 11, 972 (2021).","journal-title":"Biomolecules"},{"key":"8734_CR96","doi-asserted-by":"publisher","first-page":"387","DOI":"10.3389\/fnins.2019.00387","volume":"13","author":"VS Krishnan","year":"2019","unstructured":"Krishnan, V. S. et al. Multimodal evaluation of TMS - induced somatosensory plasticity and behavioral recovery in rats with contusion spinal cord injury. Front. Neurosci. 13, 387 (2019).","journal-title":"Front. Neurosci."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08734-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08734-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08734-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T01:02:30Z","timestamp":1761094950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08734-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":96,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8734"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08734-0","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]},"assertion":[{"value":"15 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1489"}}