Krityakiarana Warin, Sompup Kamonrapat, Jongkamonwiwat Nopporn, Mukda Sujira, Pinilla Fernando Gomez, Govitrapong Piyarat, Phansuwan-Pujito Pansiri
Division of Physical Therapy, Faculty of Health Science, Srinakharinwirot University, Nakhon-Nayok, Thailand.
Department of Rehabilitation for Persons with Disabilities, Ratchasuda College, Mahidol University, Nakhonpathom, Thailand.
J Neurosci Res. 2016 Dec;94(12):1451-1459. doi: 10.1002/jnr.23930. Epub 2016 Sep 26.
The present work aimed at analyzing the effects of melatonin on scar formation after spinal cord injury (SCI). Upregulation of reactive astrocyte under SCI pathological conditions has been presented in several studies. It has been proved that the crucial factor in triggering this upregulation is proinflammatory cytokines. Moreover, scar formation is an important barrier to axonal regeneration through the lesion area. Melatonin plays an important role in reducing inflammation, but its effects on scar formation in the injured spinal cord remain unknown. Hence, we used the model of severe crush injury in mice to investigate the effects of melatonin on scar formation. Mice were randomly separated into four groups; SCI, SCI+Melatonin 1 (single dose), SCI+Melatonin 14 (14 daily doses), and control. Melatonin was administered by intraperitoneal injection (10 mg/kg) after injury. Immunohistochemical analysis, Western blot, and behavioral evaluation were used to explore the effects of melatonin after SCI for 14 days. The melatonin-treated mice presented higher expression of neuronal markers (P < 0.001). Remarkably, the inflammatory response appeared to be greatly reduced in the SCI+Melatonin 14 group (P < 0.001), which also displayed less scar formation (P < 0.05). These findings suggest that melatonin inhibits scar formation by acting on inflammatory cytokines after SCI. Overall, our results suggest that melatonin is a promising treatment strategy after SCI that deserves further investigation. © 2016 Wiley Periodicals, Inc.
本研究旨在分析褪黑素对脊髓损伤（SCI）后瘢痕形成的影响。多项研究表明，在SCI病理条件下反应性星形胶质细胞会上调。已证实引发这种上调的关键因素是促炎细胞因子。此外，瘢痕形成是轴突通过损伤区域再生的重要障碍。褪黑素在减轻炎症方面发挥重要作用，但其对脊髓损伤后瘢痕形成的影响尚不清楚。因此，我们使用小鼠严重挤压伤模型来研究褪黑素对瘢痕形成的影响。将小鼠随机分为四组：SCI组、SCI+褪黑素1组（单剂量）、SCI+褪黑素14组（每日剂量，共14天）和对照组。损伤后通过腹腔注射给予褪黑素（10 mg/kg）。采用免疫组织化学分析、蛋白质印迹法和行为评估来探究SCI 14天后褪黑素的作用效果。褪黑素处理的小鼠神经元标志物表达较高（P < 0.001）。值得注意的是，SCI+褪黑素14组的炎症反应明显减轻（P < 0.001），瘢痕形成也较少（P < 0.05）。这些发现表明，褪黑素通过作用于SCI后的炎性细胞因子来抑制瘢痕形成。总体而言，我们的结果表明，褪黑素是SCI后一种有前景的治疗策略，值得进一步研究。© 2016威利期刊公司
