PMID- 17235293
OWN - NLM
STAT- MEDLINE
DCOM- 20070629
LR  - 20220223
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 14
IP  - 7
DP  - 2007 Apr
TI  - Neuroprotective effect of adenoviral-mediated gene transfer of TIMP-1 and -2 in 
      ischemic brain injury.
PG  - 621-5
AB  - 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.
FAU - Magnoni, S
AU  - Magnoni S
AD  - Centre for Neuroscience Research, University of Edinburgh, Edinburgh, UK. 
      smagnoni@policlinico.mi.it
FAU - Baker, A
AU  - Baker A
FAU - Thomson, S
AU  - Thomson S
FAU - Jordan, G
AU  - Jordan G
FAU - George, S J
AU  - George SJ
FAU - McColl, B W
AU  - McColl BW
FAU - McCulloch, J
AU  - McCulloch J
FAU - Horsburgh, K
AU  - Horsburgh K
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070118
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Blotting, Western/methods
MH  - Corpus Striatum/chemistry/metabolism
MH  - Gene Expression
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/*administration & dosage/genetics
MH  - Injections
MH  - Ischemic Attack, Transient/metabolism/pathology/*therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/metabolism/pathology/virology
MH  - Tissue Inhibitor of Metalloproteinase-1/analysis/*genetics/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/analysis/*genetics/metabolism
MH  - Transduction, Genetic/methods
MH  - beta-Galactosidase/genetics
EDAT- 2007/01/20 09:00
MHDA- 2007/06/30 09:00
CRDT- 2007/01/20 09:00
PHST- 2007/01/20 09:00 [pubmed]
PHST- 2007/06/30 09:00 [medline]
PHST- 2007/01/20 09:00 [entrez]
AID - 3302894 [pii]
AID - 10.1038/sj.gt.3302894 [doi]
PST - ppublish
SO  - Gene Ther. 2007 Apr;14(7):621-5. doi: 10.1038/sj.gt.3302894. Epub 2007 Jan 18.