{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:40:20Z","timestamp":1777927220165,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"15","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>After a severe, high-level spinal cord injury (SCI), plasticity to intraspinal circuits below injury results in heightened spinal sympathetic reflex activity and detrimentally impacts peripheral organ systems. Such sympathetic hyperreflexia is immediately apparent as an episode of autonomic dysreflexia (AD), a life-threatening condition characterized by sudden hypertension and reflexive bradycardia following below-level sensory inputs; for example, pressure sores or impacted fecal matter. Over time, plasticity within the spinal sympathetic reflex (SSR) circuit contributes to the progressive intensification of AD events, as the frequency and severity of AD events increase greatly beginning \u223c2 weeks post-injury (wpi). The neuroimmune system has been implicated in driving sympathetic hyperreflexia, as inhibition of the cytokine soluble tumor necrosis factor-alpha (sTNF\u03b1) using the biological mimetic XPro1595 beginning within days post-SCI has been shown to attenuate the development of AD. Here, we sought to further understand the effective therapeutic time window of XPro1595 to diminish sympathetic hyperreflexia, as indicated by AD. We delayed the commencement of continuous intrathecal administration of XPro1595 until 2 weeks after a complete, thoracic level 3 injury in adult rats. We examined the severity of colorectal distension-induced AD biweekly. We found that initiation of sTNF\u03b1 inhibition at 2 wpi does not attenuate the severity or intensification of sympathetic hyperreflexia compared with saline-treated controls. Coupled with previous data from our group, these findings suggest that central sTNF\u03b1 signaling must be targeted prior to 2 weeks post-SCI in order to decrease sympathetic hyperreflexia.<\/jats:p>","DOI":"10.1089\/neu.2020.7504","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T01:54:27Z","timestamp":1609811667000},"page":"2186-2191","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacological Inhibition of Soluble Tumor Necrosis Factor-Alpha Two Weeks after High Thoracic Spinal Cord Injury Does Not Affect Sympathetic Hyperreflexia"],"prefix":"10.1177","volume":"38","author":[{"given":"Micaela L.","family":"O'Reilly","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Mironets","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana M.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kallon","family":"Crowther","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Collyer","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Bethea","sequence":"additional","affiliation":[{"name":"Department of Biology, Drexel University, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica J.","family":"Tom","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3101729"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.62.5.473"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2017.05.002"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2004.21.1371"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3100867"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(05)52017-X"},{"issue":"12","key":"e_1_3_4_8_2","first-page":"970","article-title":"Autonomic dysreflexia causes chronic immune suppression after spinal cord injury","volume":"33","author":"Zhang Y.","year":"2013","unstructured":"Zhang Y., , Guan Z., , Reader B., , Shawler T., , Mandrekar-Colucci S., , Huang K., , Weil Z., , Bratasz A., , Wells J., , Powell N.D., , Sheridan J.F., , Whitacre C.C., , Rabchevsky A.G., , Nash M.S., , and Popovich P.G. 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