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坐骨神经移植和 FGF-2 接种促进脊髓横断大鼠运动行为改善和纤维再生。

Sciatic nerve grafting and inoculation of FGF-2 promotes improvement of motor behavior and fiber regrowth in rats with spinal cord transection.

机构信息

Laboratory of Neuroanatomy, Department of Morphology, Bioscience Center, Federal University of Rio Grande do Norte, Natal-RN, Brazil.

出版信息

Restor Neurol Neurosci. 2012;30(3):265-75. doi: 10.3233/RNN-2012-110184.

DOI:10.3233/RNN-2012-110184
PMID:22555431
Abstract

PURPOSE

Failure of severed adult central nervous system (CNS) axons to regenerate could be attributed with a reduced intrinsic growing capacity. Severe spinal cord injury is frequently associated with a permanent loss of function because the surviving neurons are impaired to regrow their fibers and to reestablish functional contacts. Peripheral nerves are known as good substrate for bridging CNS trauma with neurotrophic factor addition. We evaluated whether fibroblastic growth factor 2 (FGF-2) placed in a gap promoted by complete transection of the spinal cord may increase the ability of sciatic nerve graft to enhance motor recovery and fibers regrow.

METHODS

We used a complete spinal cord transection model. Rats received a 4 mm-long gap at low thoracic level and were repaired with saline (control) or fragment of the sciatic nerve (Nerve) or FGF-2 was added to nerve fragment (Nerve+FGF-2) to the grafts immediately after complete transection. The hind limbs performance was evaluated weekly for 8 weeks by using motor behavior score (BBB) and sensorimotor tests-linked to the combined behavior score (CBS), which indicate the degree of the motor improvement and the percentage of functional deficit, respectively. Neuronal plasticity were evaluated at the epicenter of the injury using MAP-2 and GAP-43 expression.

RESULTS

Spinal cord treatment with sciatic nerve and sciatic nerve plus FGF-2 allowed recovery of hind limb movements compared to control, manifested by significantly higher behavioral scores. Higher amounts of MAP-2 and GAP-43 immunoreactive fibers were found in the epicenter of the graft when FGF-2 was added.

CONCLUSIONS

FGF-2 added to the nerve graft favored the motor recovery and fiber regrowth. Thus, these results encourage us to explore autologous transplantation as a novel and promising cell therapy for treatment of spinal cord lesion.

摘要

目的

切断的成人中枢神经系统 (CNS) 轴突的再生失败可能归因于内在生长能力的降低。严重的脊髓损伤常伴有功能的永久性丧失,因为存活的神经元受损,无法使纤维再生并重新建立功能接触。外周神经被认为是桥接 CNS 创伤与神经营养因子添加的良好基质。我们评估了在完全横断脊髓形成的间隙中放置成纤维细胞生长因子 2 (FGF-2) 是否可以增加坐骨神经移植物增强运动恢复和纤维再生的能力。

方法

我们使用完全性脊髓横断模型。大鼠在胸段接受 4mm 长的间隙,并接受盐水(对照)或坐骨神经片段(神经)或 FGF-2 添加到神经片段(神经+FGF-2)修复,立即在完全横断后进行移植物。通过运动行为评分 (BBB) 和与综合行为评分 (CBS) 相关的感觉运动测试每周评估后肢性能 8 周,分别表示运动改善程度和功能缺陷百分比。使用 MAP-2 和 GAP-43 表达在损伤中心评估神经元可塑性。

结果

与对照组相比,脊髓用坐骨神经和坐骨神经加 FGF-2 处理允许后肢运动恢复,表现为行为评分明显更高。当添加 FGF-2 时,在移植物中心发现了更多的 MAP-2 和 GAP-43 免疫反应性纤维。

结论

添加到神经移植物中的 FGF-2 有利于运动恢复和纤维再生。因此,这些结果鼓励我们探索自体移植作为治疗脊髓损伤的一种新的有前途的细胞治疗方法。

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