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Targeted Retrograde Gene Delivery into the Injured Spinal Cord Using Recombinant Adenovirus Vector Carrying Neurotrophic Factor Gene

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Neuroprotection and Regeneration of the Spinal Cord

Abstract

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. AdV-BDNF gene or AdV-β-galactosidase (AdV-LacZ) gene was injected into the sternomastoid muscle immediately after traumatic C4 spinal cord injury. Localization of β-galactosidase expression produced by LacZ gene or AdV-BDNF gene transfection was examined by immunofluorescence staining and double staining of cell markers (NeuN, RIP, GFAP, OX-42, and NG2) in the injured spinal cord. TUNEL-positive cells were counted, and immunoreactivity to active caspase-3 and NG2 was examined after gene injection. Retrograde delivery of LacZ marker gene was identified in cervical spinal cord neurons and glial cells including oligodendrocytes in the white matter. AdV-BDNF transfection resulted in a significant decrease in the number of TUNEL-positive apoptotic cells by downregulating the caspase apoptotic pathway, with significant promotion of NG2 expression in injured spinal cord, compared with AdV-LacZ injection. Our results suggest that targeted retrograde BDNF gene delivery suppresses apoptosis of neurons and oligodendrocytes in the injured rat spinal cord.

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Acknowledgment

 This work was supported in part by Grants-in-Aid for General Scientific Research of the Ministry of Education, Science and Culture of Japan (grants numbers C15591571, B16390435, B18390411, and B19791023).

Conflict of Interest  All authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Faculty of Medical Sciences, Department of Orthopaedics and Rehabilitation Medicine, University of Fukui, Matsuoka Shimoaizuki 23-3, Eiheiji, Fukui, 910-1193, Japan

    Hideaki Nakajima, Kenzo Uchida, Takafumi Yayama, Kazuya Honjoh, Takumi Sakamoto & Hisatoshi Baba

Authors
  1. Hideaki Nakajima
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  2. Kenzo Uchida
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  3. Takafumi Yayama
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  4. Kazuya Honjoh
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  5. Takumi Sakamoto
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  6. Hisatoshi Baba
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Correspondence to Hideaki Nakajima .

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Editors and Affiliations

  1. Dept of Orthop & Rehabilit Med, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui, Japan

    Kenzo Uchida

  2. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan

    Masaya Nakamura

  3. Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Hiroshi Ozawa

  4. Department of Orthopedic Surgery, Faculty of Medicine The University of Tokushima, Tokushima, Tokushima, Japan

    Shinsuke Katoh

  5. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan

    Yoshiaki Toyama

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Nakajima, H., Uchida, K., Yayama, T., Honjoh, K., Sakamoto, T., Baba, H. (2014). Targeted Retrograde Gene Delivery into the Injured Spinal Cord Using Recombinant Adenovirus Vector Carrying Neurotrophic Factor Gene. In: Uchida, K., Nakamura, M., Ozawa, H., Katoh, S., Toyama, Y. (eds) Neuroprotection and Regeneration of the Spinal Cord. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54502-6_16

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  • DOI: https://doi.org/10.1007/978-4-431-54502-6_16

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  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54501-9

  • Online ISBN: 978-4-431-54502-6

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