Abstract |
Gene therapy may be a promising approach for treatment of brain ischemia. We and others previously demonstrated that increased activity of matrix metalloproteinases ( MMPs) contributes to the tissue damage that results from ischemic injury. The proteolysis of MMPs is tightly controlled by tissue inhibitors of MMPs (TIMPs). In this study, we examined whether adenoviral-mediated gene transfer of TIMP-1 and TIMP-2 could protect against neuronal damage induced by global cerebral ischemia in mice. An adenovirus expressing TIMP-1 or TIMP-2 (AdTIMP-1 or AdTIMP-2) or a control adenovirus (RAd60) or vehicle was injected into the striatum 3 days before transient global cerebral ischemia. The extent of neuronal damage was quantified 3 days post- ischemia. There was no significant difference in the extent of neuronal damage in vehicle as compared to RAd60-treated mice. In contrast, neuronal damage was reduced, by approximately 50%, after gene transfer of AdTIMP-1 (P<0.001) and AdTIMP-2 (P< 0.01) as compared to controls. This study provides the first in vivo evidence of the protective effects of TIMP-1 and TIMP-2 via gene transfer in global ischemia.
|
Authors | S Magnoni, A Baker, S Thomson, G Jordan, S J George, B W McColl, J McCulloch, K Horsburgh |
Journal | Gene therapy
(Gene Ther)
Vol. 14
Issue 7
Pg. 621-5
(Apr 2007)
ISSN: 0969-7128 [Print] England |
PMID | 17235293
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Tissue Inhibitor of Metalloproteinase-1
- Tissue Inhibitor of Metalloproteinase-2
- beta-Galactosidase
|
Topics |
- Adenoviridae
(genetics)
- Animals
- Blotting, Western
(methods)
- Corpus Striatum
(chemistry, metabolism)
- Gene Expression
- Genetic Therapy
(methods)
- Genetic Vectors
(administration & dosage, genetics)
- Injections
- Ischemic Attack, Transient
(metabolism, pathology, therapy)
- Male
- Mice
- Mice, Inbred C57BL
- Neurons
(metabolism, pathology, virology)
- Tissue Inhibitor of Metalloproteinase-1
(analysis, genetics, metabolism)
- Tissue Inhibitor of Metalloproteinase-2
(analysis, genetics, metabolism)
- Transduction, Genetic
(methods)
- beta-Galactosidase
(genetics)
|