Hepatocyte growth factor incorporated into herpes simplex virus vector accelerates facial nerve regeneration after crush injury

Hepatocyte growth factor incorporated into herpes simplex virus vector accelerates facial nerve regeneration after crush injury
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DOI:
10.1038/gt.2011.57
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发表时间:
2011-11-01
期刊:
影响因子:
5.1
通讯作者:
Murakami, S.
Murakami, S.
中科院分区:
医学3区
文献类型:
--
作者:
Esaki, S.;Kitoh, J.;Murakami, S.

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肝细胞生长因子(HGF)促进中枢神经系统的再生,但其对周围神经系统的影响尚不清楚。本研究旨在探讨肝细胞生长因子对小鼠面神经挤压伤后再生的影响。为此,制备了掺入HGF的复制缺陷型单纯疱疹病毒载体(HSV-HGF)。用蚊式止血钳压迫面神经主干,然后将HSV-HGF、对照载体或培养基施加于压迫的神经。我们发现,HGF组的小鼠从神经压迫中完全恢复所需的天数明显减少。此外,诱发颊肌复合动作电位的幅度增加后HSV-HGF应用。用酶联免疫法和免疫组化法检测压迫神经内及周围组织中HGF的表达。此外,在受损神经周围导入HSV-HGF显著加速了面神经功能的恢复。这些数据表明,肝细胞生长因子在促进神经损伤后的面神经再生的可能作用。此外,这种病毒递送方法可以在临床上应用于面神经减压手术期间的许多类型的严重面神经麻痹。Gene Therapy(2011)18,1063-1069; doi:10.1038/gt.2011.57; 2011年5月12日在线发表
Hepatocyte growth factor (HGF) promotes regeneration of the central nervous system, but its effects on the peripheral nervous system remain unclear. This study was conducted to elucidate the effect of HGF on regeneration of the murine facial nerve after crush injury. To do so, a replication-defective herpes simplex virus vector that incorporated HGF was prepared (HSV-HGF). The main trunk of the facial nerve was compressed by mosquito hemostats, and HSV-HGF, control vector or medium was then applied to the compressed nerve. We found that mice in the HGF group required significantly fewer days for complete recovery from nerve compression. Furthermore, the amplitude of the evoked buccinator muscle compound action potential increased following HSV-HGF application. HGF expression in and around the compressed nerve was demonstrated by enzyme-linked immunoassay and immunohistochemistry. In addition, HSV-HGF introduction around the damaged nerve significantly accelerated recovery of function of the facial nerve. These data suggest a possible role of HGF in promoting facial nerve regeneration after nerve damage. Furthermore, this viral delivery method may be applied clinically for many types of severe facial palsy during facial nerve decompression surgery. Gene Therapy (2011) 18, 1063-1069; doi:10.1038/gt.2011.57; published online 12 May 2011