Post-stroke mRNA expression profile of MMPs: effect of genetic deletion of MMP-12

Abstract

Background and purposeRecent 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.MethodsFocal 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.ResultsAlthough 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.ConclusionsIn 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.

Dexmedetomidine Increases MMP-12 and MBP Concentrations after Coronary Artery Bypass Graft Surgery with Extracorporeal Circulation Anaesthesia without Impacting Cognitive Function: A Randomised Control Trial

“…The literature reveals that higher MMP-12 levels have been associated with worse neurological outcome [ 25 ]. MMP-12 upregulation has also been associated with brain ischemia in animal models, with post-ischemic induction higher for MMP-12 than for any other MMPs [ 40 , 41 ]. Other studies have demonstrated that MMP-12 induces brain injury by damaging the BBB after focal cerebral ischemia, while MMP-12 knockdown attenuates this effect [ 15 , 42 ].…”

Bioactive Flavonoids Icaritin and Icariin Protect against Cerebral Ischemia–Reperfusion-Associated Apoptosis and Extracellular Matrix Accumulation in an Ischemic Stroke Mouse Model

“…The progression of ischemic stroke can induce the activation of stress signals, hypoxia, oxygen–glucose deprivation, and oxidative/nitrosative stress, leading to further neuro-inflammation and fibrosis in the brains [ 8 ]. As the stroke clot is removed, the reperfusion injury may refer to the reactive oxygen species (ROS)/reactive nitrogen species (RNS) response; protein expression of EMC; and its associated proteins such as matrix metalloproteinases [ 42 , 43 ], basement membrane changes [ 44 ], and inflammation induction [ 45 ]. Sun et al [ 17 ] have indicated that ICT pretreatment effectively prevents the neuroinflammatory response and oxidative damage in the brains of cerebral ischemia–reperfusion mice.…”

A Review on the Mechanisms of Stroke-Induced Muscle Atrophy

“…Notably, MMPs have also been implicated in ischemic stroke, with certain MMP gene polymorphisms conferring heightened vulnerability to cerebral ischemia [101,102]. The expression of MMPs appears to be upregulated following episodes of cerebral ischemia [103,104]. Although the relationship between stroke and MMP expression has been well studied, additional studies are needed to determine whether MMP levels following cerebral ischemia correlate with the magnitude of poststroke muscle atrophy.…”