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We, therefore, investigated the effects of intrathecal Shh-administration in the subacute phase after thoracic spinal cord injury (SCI) on secondary injury processes in rats.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Twenty-one Wistar rats were subjected to thoracic clip-contusion\/compression SCI at T9. Animals were randomized into three treatment groups (Shh, Vehicle, Sham). Seven days after SCI, osmotic pumps were implanted for seven-day continuous intrathecal administration of Shh. Basso, Beattie and Bresnahan (BBB) score, Gridwalk test and bodyweight were weekly assessed. Animals were sacrificed six\u00a0weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 was considered significant).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The intrathecal administration of Shh led to significantly increased polarization of macrophages toward the anti-inflammatory M2-phenotype, significantly decreased T-lymphocytic invasion and significantly reduced resident microglia six\u00a0weeks after the injury. Reactive astrogliosis was also significantly reduced while changes in size of the posttraumatic cyst as well as the overall macrophagic infiltration, although reduced, remained insignificant. Finally, with the administration of Shh, gain of bodyweight (216.6\u2009\u00b1\u20093.65\u00a0g vs. 230.4\u2009\u00b1\u20095.477\u00a0g; <jats:italic>p<\/jats:italic>\u2009=\u20090.0111) and BBB score (8.2\u2009\u00b1\u20090.2 vs. 5.9\u2009\u00b1\u20090.7 points; p\u2009=\u20090.0365) were significantly improved compared to untreated animals six weeks after SCI as well.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six\u00a0weeks after severe contusion\/compression SCI.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00586-021-06796-2","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T07:02:30Z","timestamp":1615446150000},"page":"1509-1520","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Sonic Hedgehog modulates the inflammatory response and improves functional recovery after spinal cord injury in a thoracic contusion\u2013compression model"],"prefix":"10.1007","volume":"30","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8218-9243","authenticated-orcid":false,"given":"Alexander","family":"Younsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoli","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Tail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Kathrin","family":"Harms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Hatami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Skutella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Unterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Zweckberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"6796_CR1","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1017\/S0317167100014530","volume":"40","author":"JC Furlan","year":"2013","unstructured":"Furlan JC, Sakakibara BM, Miller WC, Krassioukov AV (2013) Global incidence and prevalence of traumatic spinal cord injury. 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