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, Koji Abe

Research output: Contribution to journalArticle

49 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 languageEnglish
Pages (from-to)140-145
Number of pages6
JournalBrain Research
Volume947
Issue number1
DOIs
Publication statusPublished - Aug 23 2002

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Middle Cerebral Artery Infarction
Adenoviridae
Genes
Caspase 3
Reperfusion
Therapeutics
Lac Operon
Caspase 9
In Situ Nick-End Labeling
Escherichia coli
Proteins

Keywords

  • Ischemia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Therapeutic time window of adenovirus-mediated GDNF gene transfer after transient middle cerebral artery occlusion in rat. / Zhang, W. R.; Sato, K.; Iwai, M.; Nagano, I.; Manabe, Y.; Abe, Koji.

In: Brain Research, Vol. 947, No. 1, 23.08.2002, p. 140-145.

Research output: Contribution to journalArticle

Zhang, W. R. ; Sato, K. ; Iwai, M. ; Nagano, I. ; Manabe, Y. ; Abe, Koji. / Therapeutic time window of adenovirus-mediated GDNF gene transfer after transient middle cerebral artery occlusion in rat. In: Brain Research. 2002 ; Vol. 947, No. 1. pp. 140-145.
@article{2ad793e3fabd4293b0f451b10a7dd76a,
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 Koji Abe",
year = "2002",
month = "8",
day = "23",
doi = "10.1016/S0006-8993(02)02923-2",
language = "English",
volume = "947",
pages = "140--145",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Therapeutic time window of adenovirus-mediated GDNF gene transfer after transient middle cerebral artery occlusion in rat

AU - Zhang, W. R.

AU - Sato, K.

AU - Iwai, M.

AU - Nagano, I.

AU - Manabe, Y.

AU - Abe, Koji

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.

KW - Ischemia

UR - http://www.scopus.com/inward/record.url?scp=0037162971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037162971&partnerID=8YFLogxK

U2 - 10.1016/S0006-8993(02)02923-2

DO - 10.1016/S0006-8993(02)02923-2

M3 - Article

C2 - 12144862

AN - SCOPUS:0037162971

VL - 947

SP - 140

EP - 145

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -