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Abstract
Background and purpose Recent reports from our laboratory demonstrated the post-ischaemic expression profile of various matrix metalloproteinases (MMPs) in rats and the detrimental role of MMP-12 in post-stroke brain damage. We hypothesise that the post-stroke dysregulation of MMPs is similar across species and that genetic deletion of MMP-12 would not affect the post-stroke expression of other MMPs. We tested our hypothesis by determining the pre-ischaemic and post-ischaemic expression profile of MMPs in wild-type and MMP-12 knockout mice.
Methods Focal cerebral ischaemia was induced in wild-type and MMP-12 knockout mice by middle cerebral artery occlusion procedure by insertion of a monofilament suture. One hour after ischaemia, reperfusion was initiated by removing the monofilament. One day after reperfusion, ischaemic brain tissues from various groups of mice were collected, and total RNA was isolated and subjected to cDNA synthesis followed by PCR analysis.
Results Although the post-stroke expression profile of MMPs in the ischaemic brain of mice is different from rats, there is a clear species similarity in the expression of MMP-12, which was found to be predominantly upregulated in both species. Further, the post-stroke induction or inhibition of various MMPs in MMP-12 knockout mice is different from their respective expression profile in wild-type mice. Moreover, the brain mRNA expression profile of various MMPs in MMP-12 knockout mice under normal conditions is also different to their expression in wild-type mice.
Conclusions In the ischaemic brain, MMP-12 upregulates several fold higher than any other MMP. Mice derived with the genetic deletion of MMP-12 are constitutive and have altered MMP expression profile both under normal and ischaemic conditions.
- matrix metalloproteinase
- stroke
- ischemia
- reperfusion
- knockout
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Footnotes
Contributors KKV was involved in the conception and hypotheses delineation, design and execution of the study, analysis and interpretation of results. KRN was involved in animal handling, postsurgical animal care, collection of tissues, conduct of PCR analysis, acquisition and quantification of the data, statistical analysis and manuscript preparation. BC induced ischaemia in animals. IBM and DNF assisted KRN in PCR analysis. AM and IV assisted KRN in agarose gel electrophoresis. JDK, DMP, KMB and KKV reviewed and edited the manuscript.
Funding This work was supported by the Illinois Neurological Institute, OSF HealthCare Foundation.
Competing interests None declared.
Patient consent Not required.
Ethics approval The Institutional Animal Care and Use Committee of the University of Illinois College of Medicine at Peoria.
Provenance and peer review Commissioned by the CSA; externally peer reviewed.
Data sharing statement The authors agree to provide upon request the unpublished data that include raw data, metadata and statistical analysis results for the purposes of reproducing the results.