Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents ischemic brain injury after transient middle cerebral artery occlusion in rats.

Abstract

To examine a possible protective effect of exogenous glial cell line-derived neurotrophic factor (GDNF) gene expression against ischemic brain injury, a replication-defective adenoviral vector containing GDNF gene (Ad-GDNF) was directly injected into the cerebral cortex at 1 day before 90 minutes of transient middle cerebral artery occlusion (MCAO) in rats. 2,3,5-Triphenyltetrazolium chloride staining showed that infarct volume of the Ad-GDNF-injected group at 24 hours after the transient MCAO was significantly smaller than that of vehicle- or Ad-LacZ-treated group. Enzyme-linked immunosorbent assay (ELISA) for immunoreactive GDNF demonstrated that GDNF gene products in the Ad-GDNF-injected group were higher than those of vehicle-treated group at 24 hours after transient MCAO. Immunoreactive GDNF staining was obviously detected in the cortex around the needle track just before or 24 hours after MCAO in the Ad-GDNF group, whereas no or slight GDNF staining was detected in the vehicle group. The numbers of TUNEL, immunoreactive caspase-3, and cytochrome c-positive neurons induced in the ipsilateral cerebral cortex at 24 hours after transient MCAO were markedly reduced by the Ad-GDNF group. These results suggest that the successful exogenous GDNF gene transfer ameliorates ischemic brain injury after transient MCAO in association with the reduction of apoptotic signals.

• Authors: H Kitagawa, C Sasaki, K Sakai, A Mori, Y Mitsumoto, T Mori, Y Fukuchi, Y Setoguchi, K Abe
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 19 Issue 12 Pg. 1336-44 (Dec 1999) ISSN: 0271-678X [Print] United States
• PMID: 10598938 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adenoviruses, Human
• Animals
• Brain (pathology)
• Cell Line
• Cerebral Cortex
• Gene Transfer Techniques
• Genetic Vectors
• Glial Cell Line-Derived Neurotrophic Factor
• Humans
• Ischemic Attack, Transient (pathology, physiopathology, therapy)
• Male
• Middle Cerebral Artery
• Nerve Growth Factors
• Nerve Tissue Proteins (analysis, genetics, physiology)
• Rats
• Rats, Wistar
• Recombinant Proteins (analysis)
• Reperfusion
• Time Factors