Gamma knife irradiation of injured sciatic nerve induces histological and behavioral improvement in the rat neuropathic pain model.

Gamma knife irradiation of injured sciatic nerve induces histological and behavioral improvement in the rat neuropathic pain model.
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DOI:
10.1371/journal.pone.0061010
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Kawakami Y
Kawakami Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yagasaki Y;Hayashi M;Tamura N;Kawakami Y

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采用大鼠坐骨神经部分结扎(PSL)模型,观察伽玛刀(GK)照射对神经损伤的影响。在结扎后1周进行GK照射,并在结扎后3周制备神经标本。已知GK照射可诱导免疫应答,例如中枢神经系统中的神经胶质细胞活化。因此,我们确定GK照射对巨噬细胞的影响,使用免疫印迹和组织化学分析。Iba-1蛋白的表达,巨噬细胞的标志物,进一步增加在GK治疗损伤的神经相比,非辐射损伤的神经。免疫组织化学研究表明,在GK照射损伤的坐骨神经Iba-1阳性巨噬细胞的积累,以加强在该地区的远端结扎点。在相同的区域,髓鞘碎片也更有效地清除GK照射。巨噬细胞清除髓鞘碎片被认为有助于轴突生长的环境。在免疫印迹研究中,GK照射显著增加β III-微管蛋白和髓鞘蛋白零的表达,这分别是轴突再生和髓鞘再形成的标志物。甲苯胺蓝染色显示,与未照射损伤的神经相比,GK照射损伤的神经近端部位的有髓纤维直径较大,远端部位的有髓纤维数量增加。这些结果表明,GK照射损伤的神经促进再生和髓鞘再生。在一项行为学研究中,观察到PSL大鼠接受GK照射后异常性疼痛的早期缓解。当GK诱导的异常性疼痛的缓解最初检测到,胶质细胞系源性神经营养因子(GDNF),一种有效的镇痛因子的表达,显着增加GK照射。这些结果表明GK照射通过增加GDNF来减轻异常性疼痛。本研究提供了新的证据,GK照射损伤的周围神经可能有有益的影响。
We examined the effects of gamma knife (GK) irradiation on injured nerves using a rat partial sciatic nerve ligation (PSL) model. GK irradiation was performed at one week after ligation and nerve preparations were made three weeks after ligation. GK irradiation is known to induce immune responses such as glial cell activation in the central nervous system. Thus, we determined the effects of GK irradiation on macrophages using immunoblot and histochemical analyses. Expression of Iba-1 protein, a macrophage marker, was further increased in GK-treated injured nerves as compared with non-irradiated injured nerves. Immunohistochemical study of Iba-1 in GK-irradiated injured sciatic nerves demonstrated Iba-1 positive macrophage accumulation to be enhanced in areas distal to the ligation point. In the same area, myelin debris was also more efficiently removed by GK-irradiation. Myelin debris clearance by macrophages is thought to contribute to a permissive environment for axon growth. In the immunoblot study, GK irradiation significantly increased expressions of βIII-tubulin protein and myelin protein zero, which are markers of axon regeneration and re-myelination, respectively. Toluidine blue staining revealed the re-myelinated fiber diameter to be larger at proximal sites and that the re-myelinated fiber number was increased at distal sites in GK-irradiated injured nerves as compared with non-irradiated injured nerves. These results suggest that GK irradiation of injured nerves facilitates regeneration and re-myelination. In a behavior study, early alleviation of allodynia was observed with GK irradiation in PSL rats. When GK-induced alleviation of allodynia was initially detected, the expression of glial cell line-derived neurotrophic factor (GDNF), a potent analgesic factor, was significantly increased by GK irradiation. These results suggested that GK irradiation alleviates allodynia via increased GDNF. This study provides novel evidence that GK irradiation of injured peripheral nerves may have beneficial effects.
DOI: 10.1007/bf01420308
发表时间: 1996-01-01
影响因子: 2.4
作者:
Kamiryo, T;Kassell, NF;Steiner, L
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DOI: 10.1073/pnas.85.12.4530
发表时间: 1988-06-01
影响因子: 11.1
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HOFFMAN, PN;CLEVELAND, DW
通讯作者: CLEVELAND, DW
DOI: 10.1006/bbrc.1996.1112
发表时间: 1996-07-25
影响因子: 3.1
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Imai, Y;Ibata, I;Kohsaka, S
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DOI: 10.1006/exnr.1996.0142
发表时间: 1996-09-01
影响因子: 5.3
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DOI: 10.1016/s0006-8993(96)00980-8
发表时间: 1996-12-02
期刊: BRAIN RESEARCH
影响因子: 2.9
作者:
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通讯作者: Luduena, RF