Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia

doi:10.1016/S0304-3940(97)00859-8

Neuroscience Letters

Volume 238, Issues 1–2, 28 November 1997, Pages 53-56

https://doi.org/10.1016/S0304-3940(97)00859-8 Get rights and content

Abstract

Matrix metalloproteinases (MMPs) are involved in remodelling extracellular matrix. Gelatinase B (MMP-9) is an inducible 92 kDa MMP expressed by neutrophils, microglia, and endothelial cells. Gelatinase A (MMP-2) is a 72 kDa MMP, constitutively expressed in brain. Elevated MMP activity has been linked to various pathologic conditions, and the therapeutic benefit of MMP inhibitors is under study in a few experimental models. Using gelatin zymography, we have compared activities of these MMPs in infarcted and matched non-infarcted cerebral tissue from eight subjects dying at intervals of less than 2 h to several years after a stroke. Gelatinase B activity was markedly elevated in the infarcted tissue at two days post-infarction, and remained elevated in cases dying months after the event. Increases in gelatinase A activity were subtle at 2–5 days; they were marked and significant in cases dying at 4 months and later. The findings indicate distinct temporal profiles of post-ischemic gelatinase activity in human brain, with earlier but equally persistent elevation in gelatinase B when compared to gelatinase A.

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Acknowledgements

The authors thank Drs. Roland Auer and Alistair Buchan for their insightful comments on this study, and Dr. Tak Fung for his able advice on statistical analysis of the data.

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The pre-treatment with aeTA for 15 days exhibited significant improvement in neurological outcome and reduced infarct volume compared with the MCAo rats. The aeTA treatment also reduced the BBB damage which was confirmed through decreased EB extravasations, significant reduction in protein levels of MMPs (MMP2 &MMP9) and maintaining the protein levels of tight junction proteins. We also found that aeTA treatment downregulated the mRNA levels of MMPs and upregulated mRNA expression levels of TIMPs and tight junction proteins (Claudin5 & Occludin).
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The effects of memantine on the serum concentrations of matrix metalloproteinases and neurologic function of patients with ischemic stroke
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Citation Excerpt :
Matrix metalloproteinases (MMPs) are a large family of endoproteases involved in tissue destruction caused by the neuroinflammatory response after ischemic stroke [4,15]. The upregulated expression of some MMPs such as gelatinase A (MMP-2) and gelatinase B (MMP-9) after the stroke is associated with the pathogenesis of brain ischemia and failure of brain endothelial cells function in response to cerebral ischemia–reperfusion [5,16–18]. The National Institute of Health Stroke Scale (NIHSS) and Barthel Index (BI) are used to assess neurologic function.
Memantine was suggested as a promising treatment for stroke due to its neuroprotective property and efficacy in reducing ischemic brain injury and improving post-ischemic neurological recovery. This pilot, open-label, randomized clinical trial was conducted to investigate the impact of memantine on serum concentrations of matrix metalloproteinases (MMP)-2 and MMP-9, as neuronal damage biomarkers, and neurologic function evaluated by the National Institute of Health Stroke Scale (NIHSS) and Barthel index (BI) in patients with ischemic stroke. Admitted patients with mild to moderate ischemic stroke were assessed for eligibility, and eligible patients were randomized to the intervention or control group. Enrolled patients in the intervention group received 20 mg memantine every 8 h for five days and then 20 mg daily for three months. Both groups managed with the standard treatments. From 77 randomized patients, 29 participants in the control group and 24 patients in the intervention group completed the study. Data showed that the increase in the serum concentrations of MMP-9 within the first 5 days of the study was significantly lower in the intervention group (P = 0.005). This effect of memantine on the MMP-2 was not significant (P = 0.448). memantine also could significantly improve the neurologic function of the patients according to NIHSS (P < 0.0001) and BI (P = 0.002) during hospitalization and after that. In conclusion, memantine could be considered as a neuroprotective agent in patients with mild to moderate ischemic stroke, based on its significant effects on reducing brain damage and improving neurologic function of the patients.
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Diabetes elevates the risk of stroke, promotes inflammation, and exacerbates vascular and white matter damage post stroke, thereby hindering long term functional recovery. Here, we investigated the neurorestorative effects and the underlying therapeutic mechanisms of treatment of stroke in type 2 diabetic rats (T2DM) using exosomes harvested from bone marrow stromal cells obtained from T2DM rats (T2DM-MSC-Exo).
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Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia

Abstract

Section snippets

Acknowledgements

Thromb. Res.

J. Biol. Chem.

J. Biol. Chem.

Anal. Biochem.

Matrix Biol.

Brain Res.

Brain Res.

FEBS Lett.

Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage

Stroke

Protease production by cultured microglia: substrate gel analysis and immobilized matrix degradation

J. Neurosci. Res.

Microvascular basal lamina antigens disappear during cerebral ischemia and reperfusion

Stroke

Hemorrhagic transformation and microvascular integrity during focal cerebral ischemia/reperfusion

J. Cerebral Blood Flow Metab.