Department of Neurosurgery, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany.
Department of Neuroanatomy, Institute for Anatomy and Cell Biology, University of Heidelberg, INF 307, 69120, Heidelberg, Germany.
Eur Spine J. 2021 Jun;30(6):1509-1520. doi: 10.1007/s00586-021-06796-2. Epub 2021 Mar 11.
The Sonic Hedgehog (Shh) pathway has been associated with a protective role after injury to the central nervous system (CNS). 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.
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 weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant).
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 weeks 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 ± 3.65 g vs. 230.4 ± 5.477 g; p = 0.0111) and BBB score (8.2 ± 0.2 vs. 5.9 ± 0.7 points; p = 0.0365) were significantly improved compared to untreated animals six weeks after SCI as well.
Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six weeks after severe contusion/compression SCI.
Sonic Hedgehog（Shh）通路与中枢神经系统（CNS）损伤后的保护作用有关。因此，我们研究了鞘内给予 Shh 对大鼠胸段脊髓损伤（SCI）后亚急性期继发性损伤过程的影响。
21 只 Wistar 大鼠在 T9 处接受夹压型胸段 SCI。动物随机分为三组（Shh、Vehicle、Sham）。SCI 后 7 天，植入渗透泵进行 7 天持续鞘内 Shh 给药。每周评估 Basso、Beattie 和 Bresnahan（BBB）评分、网格行走试验和体重。SCI 后 6 周处死动物，并进行免疫组织化学分析。组间比较结果并进行统计学分析（p<0.05 为有统计学意义）。
鞘内给予 Shh 可显著增加巨噬细胞向抗炎 M2 表型极化，显著减少 T 淋巴细胞浸润，显著减少损伤后 6 周的小胶质细胞浸润。反应性星形胶质细胞增生也明显减少，虽然创伤后囊肿的大小变化以及总体巨噬细胞浸润减少，但仍无统计学意义。最后，给予 Shh 后，与未治疗的动物相比，SCI 后 6 周时体重增加（216.6±3.65g 比 230.4±5.477g；p=0.0111）和 BBB 评分（8.2±0.2 比 5.9±0.7 分；p=0.0365）明显改善。
鞘内给予 Shh 在严重挤压/压缩 SCI 后 6 周可减轻神经炎症、减少星形胶质细胞增生，改善功能恢复，具有神经保护作用。
