Therapeutic time window of adenovirus-mediated GDNF gene transfer after transient middle cerebral artery occlusion in rat

W. R. Zhang; K. Sato; M. Iwai; I. Nagano; Y. Manabe; K. Abe

doi:10.1016/S0006-8993(02)02923-2

Therapeutic time window of adenovirus-mediated GDNF gene transfer after transient middle cerebral artery occlusion in rat

W. R. Zhang, K. Sato, M. Iwai, I. Nagano, Y. Manabe, K. Abe

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

The time dependent influence of adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) gene (Ad-GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with Ad-GDNF significantly reduced the infarct volume when immediately administered after the reperfusion, but became insignificant when administered at 1 h after the reperfusion as were the cases treated with vehicle- and adenoviral vector containing the E. coli lacZ gene (Ad-LacZ)-treated groups. The protective effect of GDNF was related to the significant reduction of the number of TUNEL positive cells as well as immunohistochemical positive cells for active caspase-3 but not -9. These results showed that exogenous GDNF gene transfer successfully reduced the infarct size in a time-dependant manner by suppressing active caspase-3 but not active caspase-9. However, the therapeutic time window was shorter than the effect of GDNF protein itself previously reported.

Original language	English
Pages (from-to)	140-145
Number of pages	6
Journal	Brain Research
Volume	947
Issue number	1
DOIs	https://doi.org/10.1016/S0006-8993(02)02923-2
Publication status	Published - Aug 23 2002

Keywords

Ischemia

ASJC Scopus subject areas

Neuroscience(all)
Molecular Biology
Clinical Neurology
Developmental Biology

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title = "Therapeutic time window of adenovirus-mediated GDNF gene transfer after transient middle cerebral artery occlusion in rat",

abstract = "The time dependent influence of adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) gene (Ad-GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with Ad-GDNF significantly reduced the infarct volume when immediately administered after the reperfusion, but became insignificant when administered at 1 h after the reperfusion as were the cases treated with vehicle- and adenoviral vector containing the E. coli lacZ gene (Ad-LacZ)-treated groups. The protective effect of GDNF was related to the significant reduction of the number of TUNEL positive cells as well as immunohistochemical positive cells for active caspase-3 but not -9. These results showed that exogenous GDNF gene transfer successfully reduced the infarct size in a time-dependant manner by suppressing active caspase-3 but not active caspase-9. However, the therapeutic time window was shorter than the effect of GDNF protein itself previously reported.",

keywords = "Ischemia",

author = "Zhang, {W. R.} and K. Sato and M. Iwai and I. Nagano and Y. Manabe and K. Abe",

note = "Funding Information: This work was partly supported by Grants-in-Aid for Scientific Research (B) 12470141 and (Hoga) 12877211 from the Ministry of Education, Science, Culture and Sports of Japan, and by Grants (KT, YI) and Comprehensive Research on Aging and Health (H11-Choju-010, No. 207, AK) from the Ministry of Health and Welfare of Japan, and by Grants-in-Aid from Japanese–Chinese Medical Association.",

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AU - Zhang, W. R.

AU - Sato, K.

AU - Iwai, M.

AU - Nagano, I.

AU - Manabe, Y.

AU - Abe, K.

N1 - Funding Information: This work was partly supported by Grants-in-Aid for Scientific Research (B) 12470141 and (Hoga) 12877211 from the Ministry of Education, Science, Culture and Sports of Japan, and by Grants (KT, YI) and Comprehensive Research on Aging and Health (H11-Choju-010, No. 207, AK) from the Ministry of Health and Welfare of Japan, and by Grants-in-Aid from Japanese–Chinese Medical Association.

PY - 2002/8/23

Y1 - 2002/8/23

N2 - The time dependent influence of adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) gene (Ad-GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with Ad-GDNF significantly reduced the infarct volume when immediately administered after the reperfusion, but became insignificant when administered at 1 h after the reperfusion as were the cases treated with vehicle- and adenoviral vector containing the E. coli lacZ gene (Ad-LacZ)-treated groups. The protective effect of GDNF was related to the significant reduction of the number of TUNEL positive cells as well as immunohistochemical positive cells for active caspase-3 but not -9. These results showed that exogenous GDNF gene transfer successfully reduced the infarct size in a time-dependant manner by suppressing active caspase-3 but not active caspase-9. However, the therapeutic time window was shorter than the effect of GDNF protein itself previously reported.

AB - The time dependent influence of adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) gene (Ad-GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with Ad-GDNF significantly reduced the infarct volume when immediately administered after the reperfusion, but became insignificant when administered at 1 h after the reperfusion as were the cases treated with vehicle- and adenoviral vector containing the E. coli lacZ gene (Ad-LacZ)-treated groups. The protective effect of GDNF was related to the significant reduction of the number of TUNEL positive cells as well as immunohistochemical positive cells for active caspase-3 but not -9. These results showed that exogenous GDNF gene transfer successfully reduced the infarct size in a time-dependant manner by suppressing active caspase-3 but not active caspase-9. However, the therapeutic time window was shorter than the effect of GDNF protein itself previously reported.

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