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.

• Authors: W R Zhang, K Sato, M Iwai, I Nagano, Y Manabe, K Abe
• Journal: Brain research (Brain Res) Vol. 947 Issue 1 Pg. 140-5 (Aug 23 2002) ISSN: 0006-8993 [Print] Netherlands
• PMID: 12144862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gdnf protein, rat
• Glial Cell Line-Derived Neurotrophic Factor
• Nerve Growth Factors
• Nerve Tissue Proteins
• Caspases

Topics

• Adenoviridae (genetics)
• Animals
• Blotting, Western
• Brain Ischemia (pathology, therapy)
• Caspases (metabolism)
• Genetic Therapy (methods)
• Genetic Vectors
• Glial Cell Line-Derived Neurotrophic Factor
• Immunohistochemistry
• In Situ Nick-End Labeling
• Infarction, Middle Cerebral Artery (pathology)
• Male
• Middle Cerebral Artery (physiology)
• Nerve Growth Factors (genetics)
• Nerve Tissue Proteins (genetics)
• Rats
• Rats, Wistar
• Time Factors
• Transfection