Nakajima Hideaki, Uchida Kenzo, Kobayashi Shigeru, Kokubo Yasuo, Yayama Takafumi, Sato Ryuichiro, Baba Hisatoshi
Division of Orthopaedics and Rehabilitation Medicine, Department of Surgery, School of Medicine, University of Fukui, Shimoaizuki 23, Matsuoka, Fukui 910-1193, Japan.
Neurosci Lett. 2005 Sep 2;385(1):30-5. doi: 10.1016/j.neulet.2005.05.012.
Direct routes of gene administration (intrathecal, intracerebroventricular or intraparenchymal infusion) have been used for effective and sustained gene delivery, but serious concerns exist about possible traumatic injury as well as neural damage that may lead to further tissue necrosis, apoptosis and cell death. We evaluated targeted retrograde gene delivery through the sternomastoid muscle (innervated by the spinal accessory nerves) into the injured cervical spinal cord using a recombinant adenovirus vector. LacZ gene expression in the cervical spinal cord was noted from 3 days to 4 weeks after the injection of vector into the sternomastoid muscles of the rats. Recombinant adenovirus vector was transferred via a retrograde mechanism into the injured cervical spinal cord with high transduction efficacy (80.6--98.9%) over certain adenoviral titer and dosage. Transduction was less efficient when the vector was injected 1 and 2 weeks after spinal cord injury (44.2--56.8%). Our results indicate retrograde delivery of recombinant adenovirus vector is possible immediately after spinal cord injury, and that this method is promising for gene delivery because it is effective, selective, less invasive to the injured spinal cord, has long-lasting gene expression, and is potentially feasible treatment choice for spinal cord injury.
基因给药的直接途径（鞘内、脑室内或脑实质内注射）已被用于实现有效且持续的基因传递，但人们对可能的创伤性损伤以及可能导致进一步组织坏死、凋亡和细胞死亡的神经损伤存在严重担忧。我们评估了使用重组腺病毒载体通过胸锁乳突肌（由副神经支配）向损伤的颈脊髓进行靶向逆行基因传递的方法。在将载体注射到大鼠的胸锁乳突肌后3天至4周，观察到颈脊髓中有LacZ基因表达。重组腺病毒载体通过逆行机制以高转导效率（80.6%-98.9%）转移到损伤的颈脊髓中，该效率在一定腺病毒滴度和剂量范围内。在脊髓损伤后1周和2周注射载体时，转导效率较低（44.2%-56.8%）。我们的结果表明，在脊髓损伤后立即进行重组腺病毒载体的逆行传递是可行的，并且这种方法有望用于基因传递，因为它有效、具有选择性、对损伤的脊髓侵袭性较小、基因表达持久，并且可能是脊髓损伤潜在可行的治疗选择。
