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嗅鞘细胞条件培养基促进脊髓挫伤损伤后的功能恢复和轴突再生。

Conditioned medium of olfactory ensheathing cells promotes the functional recovery and axonal regeneration after contusive spinal cord injury.

作者信息

Gu Mengchao, Gao Zhengchao, Li Xiaohui, Guo Lei, Lu Teng, Li Yuhuan, He Xijing

机构信息

Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710004, China.

Department of Radiology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710004, China.

出版信息

Brain Res. 2017 Jan 1;1654(Pt A):43-54. doi: 10.1016/j.brainres.2016.10.023. Epub 2016 Oct 24.

Abstract

OBJECTIVE

To investigate the effectiveness and the potential role of olfactory ensheathing cell conditioned medium (OEC-M) to treat contusive spinal cord injury (SCI).

METHODS

The contusive SCI model was established by NYU weight-drop impactor at T10 segment. Male Sprague-Dawley rats received intraperitoneal injection of control medium (Con-M, n=18), low dose OEC-M (n=18) and high dose OEC-M (n=18). Immunofluorescence was performed to identify the purity of cultured OECs. BBB score was used to assess the functional recovery. BDNF concentrations of OEC-M, Con-M and rats plasma samples were determined by ELISA. Conventional MRI and diffusion tensor tractography (DTT) were applied to visualize the repair process of SCI. Diffusion tensor imaging (DTI) and immunohistochemistry of NF200 were carried out to evaluate the axonal regeneration.

RESULTS

After the systemic delivery of treatment, BBB scores and BDNF levels in peripheral blood were significantly higher in OEC-M treated groups than in Con-M group. MRI and DTT demonstrated a better radiological recovery after SCI in OEC-M treated groups and higher dose of OEC-M were accompanied with better outcomes. DTI and NF200 staining revealed the OEC-M treatment promoted axonal regeneration around the injury epicenter but no axonal regeneration was observed at the lesion site.

CONCLUSION

The results indicate that the OEC-M treatment improves the functional recovery and promotes the axonal regeneration around the injury epicenter after contusive SCI. This strategy represents a novel cell-free OEC based therapy to effectively treat SCI.

摘要

目的

探讨嗅鞘细胞条件培养基(OEC-M)治疗脊髓挫伤性损伤(SCI)的有效性及潜在作用。

方法

采用纽约大学重量降落撞击器在T10节段建立脊髓挫伤性损伤模型。雄性Sprague-Dawley大鼠腹腔注射对照培养基(Con-M,n = 18)、低剂量OEC-M(n = 18)和高剂量OEC-M(n = 18)。进行免疫荧光鉴定培养的嗅鞘细胞纯度。采用BBB评分评估功能恢复情况。通过酶联免疫吸附测定法(ELISA)测定OEC-M、Con-M及大鼠血浆样本中的脑源性神经营养因子(BDNF)浓度。应用传统磁共振成像(MRI)和扩散张量纤维束成像(DTT)观察脊髓损伤的修复过程。进行扩散张量成像(DTI)和神经丝200(NF200)免疫组织化学检测以评估轴突再生情况。

结果

全身给予治疗后,OEC-M治疗组的BBB评分和外周血BDNF水平显著高于Con-M组。MRI和DTT显示,OEC-M治疗组脊髓损伤后的放射学恢复情况更好,且高剂量OEC-M的效果更佳。DTI和NF200染色显示,OEC-M治疗促进了损伤中心周围的轴突再生,但在损伤部位未观察到轴突再生。

结论

结果表明,OEC-M治疗可改善脊髓挫伤性损伤后的功能恢复,并促进损伤中心周围的轴突再生。该策略代表了一种基于嗅鞘细胞的新型无细胞疗法,可有效治疗脊髓损伤。

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