{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:58:23Z","timestamp":1785463103657,"version":"3.56.0"},"reference-count":54,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Hyperreflexia associated with spasticity is a prevalent neurological condition characterized by excessive and exaggerated reflex responses to stimuli. Hyperreflexia can be caused by several diseases including multiple sclerosis, stroke and spinal cord injury (SCI). Although we have previously identified the contribution of the RAC1\u2010PAK1 pathway underlying spinal hyperreflexia with SCI\u2010induced spasticity, a feasible druggable target has not been validated. To assess the utility of targeting PAK1 to attenuate H\u2010reflex hyperexcitability, we administered Romidepsin, a clinically available PAK1 inhibitor, in Thy1\u2010YFP reporter mice. We performed longitudinal EMG studies with a study design that allowed us to assess pathological H\u2010reflex changes and drug intervention effects over time, before and after contusive SCI. As expected, our results show a significant loss of rate\u2010dependent depression \u2013 an indication of hyperreflexia and spasticity \u2013 1 month following SCI as compared with baseline, uninjured controls (or before injury). Romidepsin treatment reduced signs of hyperreflexia in comparison with control cohorts and in pre\u2010 and post\u2010drug intervention in SCI animals. Neuroanatomical study further confirmed drug response, as romidepsin treatment also reduced the presence of SCI\u2010induced dendritic spine dysgenesis on \u03b1\u2010motor neurons. Taken together, our findings extend previous work demonstrating the utility of targeting PAK1 activity in SCI\u2010induced spasticity and support the novel use of romidepsin as an effective tool for managing spasticity.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16296-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>PAK1 plays a role in contributing to the development of spinal cord injury (SCI)\u2010induced spasticity by contributing to dendritic spine dysgenesis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In this study, we explored the preclinical utility of inhibiting PAK1 to reduce spasticity and dendritic spine dysgenesis in an SCI mouse model.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Romidepsin is a PAK1 inhibitor approved in the US in 2009 for the treatment of cutaneous T\u2010cell lymphoma.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Here we show that romidepsin treatment after SCI reduced SCI\u2010induced H\u2010reflex hyperexcitability and abnormal \u03b1\u2010motor neuron spine morphology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This study provides compelling evidence that romidepsin may be a promising therapeutic approach for attenuating SCI\u2010induced spasticity.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp284976","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T13:45:43Z","timestamp":1725457543000},"page":"5061-5081","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PAK1 inhibition with Romidepsin attenuates H\u2010reflex hyperexcitability after spinal cord injury"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6933-9236","authenticated-orcid":false,"given":"Sierra D.","family":"Kauer","sequence":"first","affiliation":[{"name":"Department 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