Nakajima Hideaki, Uchida Kenzo, Kobayashi Shigeru, Inukai Tomoo, Horiuchi Yukiko, Yayama Takafumi, Sato Ryuichiro, Baba Hisatoshi
Division of Orthopaedics and Rehabilitation Medicine, Department of Surgery, University of Fukui Faculty of Medical Sciences, Fukui, Japan.
J Neurotrauma. 2007 Apr;24(4):703-12. doi: 10.1089/neu.2006.0004.
We investigated the efficacy of retrograde gene delivery via the sternomastoid muscle of recombinant adenovirus vector (AdV) carrying brain-derived neurotrophic factor (BDNF) gene for the rescue of injured rat spinal cord. One hundred-thirty five adult Sprague-Dawley rats were used in the study with a standard weight-compression technique to produce spinal cord injury. AdV-BDNF gene or AdV-beta-galactosidase (AdV-LacZ) gene was injected into the sternomastoid muscle immediately after traumatic C4 segment spinal cord injury. AdV-BDNF was successfully appeared in the injured cervical spinal cord following injection into the sternomastoid muscle. BDNF expression in the anterior horn neurons of the cervical spinal cord reached peak levels at 1-2 weeks; and the expression persisted at significant levels for approximately 4 weeks after injury. AdV-BDNF transfection was associated with increased numbers of intact neurons as confirmed by Nissl, cholineacetyltransferase (ChAT), and acetylcholine esterase (AChE) staining especially from 2 weeks after injury, compared with the AdV-LacZ injected rats. Our results suggest that in vivo targeted retrograde AdV-BDNF-gene delivery may enhance neuronal survival following traumatic injury of the spinal cord.
我们研究了通过携带脑源性神经营养因子（BDNF）基因的重组腺病毒载体（AdV）经胸锁乳突肌进行逆行基因递送对损伤大鼠脊髓的挽救作用。本研究使用135只成年Sprague-Dawley大鼠，采用标准的重量压迫技术造成脊髓损伤。在创伤性C4节段脊髓损伤后立即将AdV-BDNF基因或AdV-β-半乳糖苷酶（AdV-LacZ）基因注入胸锁乳突肌。将AdV-BDNF注入胸锁乳突肌后，其成功出现在损伤的颈脊髓中。颈脊髓前角神经元中的BDNF表达在1-2周时达到峰值水平；损伤后约4周表达持续维持在显著水平。与注射AdV-LacZ的大鼠相比，通过尼氏染色、胆碱乙酰转移酶（ChAT）和乙酰胆碱酯酶（AChE）染色证实，AdV-BDNF转染与完整神经元数量增加有关，尤其是在损伤后2周。我们的结果表明，体内靶向逆行AdV-BDNF基因递送可能会提高脊髓创伤后神经元的存活率。
