Adenovirus-mediated glial cell line-derived neurotrophic factor gene delivery reduces motor neuron injury after transient spinal cord ischemia in rabbits

Masahiro Sakurai, Koji Abe, Takeshi Hayashi, Yasuhiro Setoguchi, Gen Ya Yaginuma, Taiichiro Meguro, Koichi Tabayashi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Objective: Glial cell line-derived neurotrophic factor (GDNF) has protective effects on various injuries involving the central and peripheral nervous systems in vitro and vivo. However, the possible protective effect of GDNF on spinal cord ischemia and the exact mechanism involved in the ameliorative effect of GDNF on ischemic spinal cord injuries are not fully understood. Therefore, we investigated the possible protective effect of the adenovirus-mediated GDNF gene delivery on transient spinal cord ischemia in rabbits. Methods: The adenoviral vector (lacZ gene as a control or GDNF gene contained) was injected directly into the lumbar spinal cord via a needle inserted into the dorsal spine 2 days before the animal was subjected to 15 minutes of spinal cord ischemia induced by infrarenal aortic occlusion. In situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nickend labeling (TUNEL staining) was performed, and temporal profiles of the GDNF and caspase-3 (caspase-3 is the marker of apoptotic change) immunoreactivity were investigated. Results: In the control rabbit, the majority of motor neurons showed selective cell death at 7 days of reperfusion. Immunocytochemistry showed that in situ TUNEL staining was selectively detected at 2 days of reperfusion in motor neuron nuclei. GDNF and caspase-3 were selectively induced in the motor neuron cells at 8 hours of reperfusion. In the GDNF-treated group, a large population of motor neuron cells was still surviving at 7 days after having been subjected to 15 minutes of ischemia. Unlike the control group, the GDNF-treated group expressed GDNF persistently. Induction of TUNEL staining and immunoreactivity for caspase-3 were greatly reduced by the GDNF treatment. Conclusion: These results suggest that the reduction in motor neuron death by GDNF was greatly associated with a reduction in DNA fragmentation and apoptotic signals of the caspase-3 cascade; they further suggest a great potential for gene therapy for paraplegic patients in the future.

Original languageEnglish
Pages (from-to)1148-1157
Number of pages10
JournalJournal of Thoracic and Cardiovascular Surgery
Volume120
Issue number6
Publication statusPublished - 2000

Fingerprint

Spinal Cord Ischemia
Glial Cell Line-Derived Neurotrophic Factor
Motor Neurons
Adenoviridae
Rabbits
Wounds and Injuries
Genes
Caspase 3
In Situ Nick-End Labeling
Reperfusion
Staining and Labeling
Spinal Cord
Lac Operon
DNA Nucleotidylexotransferase
Peripheral Nervous System
DNA Fragmentation
Biotin
Spinal Cord Injuries
Genetic Therapy
Needles

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Adenovirus-mediated glial cell line-derived neurotrophic factor gene delivery reduces motor neuron injury after transient spinal cord ischemia in rabbits. / Sakurai, Masahiro; Abe, Koji; Hayashi, Takeshi; Setoguchi, Yasuhiro; Yaginuma, Gen Ya; Meguro, Taiichiro; Tabayashi, Koichi.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 120, No. 6, 2000, p. 1148-1157.

Research output: Contribution to journalArticle

Sakurai, Masahiro ; Abe, Koji ; Hayashi, Takeshi ; Setoguchi, Yasuhiro ; Yaginuma, Gen Ya ; Meguro, Taiichiro ; Tabayashi, Koichi. / Adenovirus-mediated glial cell line-derived neurotrophic factor gene delivery reduces motor neuron injury after transient spinal cord ischemia in rabbits. In: Journal of Thoracic and Cardiovascular Surgery. 2000 ; Vol. 120, No. 6. pp. 1148-1157.
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AU - Sakurai, Masahiro

AU - Abe, Koji

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AU - Setoguchi, Yasuhiro

AU - Yaginuma, Gen Ya

AU - Meguro, Taiichiro

AU - Tabayashi, Koichi

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