中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (7): 1255-1261.doi: 10.4103/1673-5374.251334

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

依布硒啉对创伤性脊髓损伤的神经保护

  

  • 出版日期:2019-07-15 发布日期:2019-07-15

Use of ebselen as a neuroprotective agent in rat spinal cord subjected to traumatic injury

Wojciech Ślusarczyk 1 , Edyta Olakowska 1 , Magdalena Larysz-Brysz 1 , Izabella Woszczycka-Korczyńska 1 , Daria Gendosz de Carrillo 1 , Władysław P. Węglarz 2 , Joanna Lewin-Kowalik 1 , Wiesław Marcol 1   

  1. 1 Department of Physiology, Medical University of Silesia, Katowice, Poland
    2 Institute of Nuclear Physics, Polish Academy of Sciences, Krakow, Poland
  • Online:2019-07-15 Published:2019-07-15
  • Contact: Wies?aw Marcol, MD, PhD, wmarcol@o2.pl.

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摘要：

研究已证明氧自由基对脊髓损伤后的继发性损害的发生起到了推动作用。为研究抗氧化剂依布硒啉对实验性SCI的神经保护作用，实验对应用球囊压迫法建立SCI大鼠模型，于伤后24h灌胃依布硒啉（10mg/kg）或不给予其他治疗。在伤后12周使用BBB量表和足迹测试评估行为变化，并进行脊髓和脑的组织病理学和免疫组化染色，以及损伤脊髓的MRI观察。与未进行治疗的SCI大鼠相比，依布硒啉治疗对SCI大鼠神经功能缺损以及脊髓病理损害的改善作用轻微，即脊髓切片中病变长度（囊肿/瘢痕）较短，但脊髓空洞面积非常相似，这种变化也得到了MRI T2加权成像和弥散加权成像的印证；依布硒啉治疗的大鼠脑干和运动皮质中FluoroGold逆行标记神经元数量高出几倍。从而表明，依布硒啉对受损脊髓有神经保护作用，但作用有限。

orcid: 0000-0002-8914-7273 (Wies?aw Marcol)

关键词: 依布硒啉, 抗氧化剂, 脊髓损伤, 氧自由基, FluoroGold逆行标记, MRI, 神经功能, 神经保护, 神经再生

Abstract:

Spinal cord injury (SCI) causes disturbances of motor skills. Free radicals have been shown to be essential for the development of spinal cord trauma. Despite some progress, until now no effective pharmacological therapies against SCI have been verified. The purpose of our experiment was to investigate the neuroprotective effects of ebselen on experimental SCI. Twenty-two rats subjected to SCI were randomly subjected to SCI with no further treatment (n = 10) or intragastric administration of ebselen (10 mg/kg) immediately and 24 hours after SCI. Behavioral changes were assessed using the Basso, Beattie, and Bresnahan locomotor scale and footprint test during 12 weeks after SCI. Histopathological and immunohistochemical analyses of spinal cords and brains were performed at 12 weeks after SCI. Magnetic resonance imaging analysis of spinal cords was also performed at 12 weeks after SCI. Rats treated with ebselen presented only limited  neurobehavioral progress as well as reduced spinal cord injuries compared with the control group, namely length of lesions (cysts/scars) visualized histopathologically in the spinal cord sections was less but cavity area was very similar. The same pattern was found in T2-weighted magnetic resonance images (cavities) and diffusion-weighted images (scars). The number of FluoroGold retrogradely labeled neurons in brain stem and motor cortex was several-fold higher in ebselen-treated rats than in the control group. The findings suggest that ebselen has only limited neuroprotective effects on injured spinal cord. All exprimental procedures were approved by the Local Animal Ethics Committee for Experiments on Animals in Katowice (Katowice, Poland) (approval No. 19/2009).

Key words: ebselen, antioxidant, neuroprotection, neuroregeneration, spinal cord injury, spinal cord repair, functional recovery