Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures

Rosenberg, Gary A.; Cunningham, Lee Anna; Wallace, James A.; Alexander, Susan; Estrada, Eduardo Y.; Grossetete, Mark; Razhagi, Abbas; Miller, Karen; Gearing, A. J. H.

doi:10.1016/s0006-8993(00)03294-7

Cited by 360 publications

(298 citation statements)

References 19 publications

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“…In normal rat tissues, MMP-2 was present in an astrocyte population near the ventricular walls, the pial surface, and the blood vessels (Rosenberg et al, 2001a). The MMP-2 was seen in the normal brain in the astrocytic processes, particularly those abutting blood vessels, ependymal, and pial cells.…”

Section: Cellular Localization Of the Mmps In Brainmentioning

confidence: 94%

“…Active forms of MMP-2 appear in the supernatant after LPS or IL-1 stimulation and significantly increased the substrate degradation, resulting in the release of MMP-2 and MMP-9 into the conditioned medium (Colton et al, 1993). Mixed microglia and astrocytes in culture produce an active form of MMP-9, when stimulated by LPS (Rosenberg et al, 2001a). Immunostaining of mixed glial cultures with an antibody to MMP-3 showed that it was expressed by microglia, but not by astrocytes.…”

Section: Studies Of Mmps In Brain Cell Culturesmentioning

confidence: 99%

“…In a rat model of permanent ischemia, MMP-9 was identified in cerebral blood vessels and in inflammatory cells (Romanic et al, 1998). The MMPs have been studied in temporary ischemia caused by 90-min occlusion of the middle cerebral artery by a suture thread with reperfusion for various times (Rosenberg et al, 2001a). Inflammatory MMPs, MMP-3, and MMP-9, were seen at 16 h of reperfusion.…”

Section: Cellular Localization Of the Mmps In Brainmentioning

confidence: 99%

“…If the ischemic injury is prolonged, a secondary reaction begins through the white blood cells (WBCs), fibrin deposition, and cytokines. Stimulation of the AP-1/NF-B sites in the promoter regions of the proinflammatory MMP genes leads to MMP-3 and -9 production, and the opening of the BBB with edema and hemorrhage (Rosenberg et al, 2001a).…”

Section: Endogenous Mmp Inhibitors: Tissue Inhibitors Of Metalloprotementioning

confidence: 99%

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Matrix metalloproteinases in neuroinflammation

Rosenberg

2002

Glia

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778

667

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Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases. Brain cells express both constitutive and inducible MMPs in response to cellular stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as inactive enzymes, the MMPs require activation by other proteases and free radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which includes the recently discovered ADAMs (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families. MPs have complex roles at the cell surface and within the extracellular matrix. At the cell surface, they act as sheddases, releasing growth factors, death receptors, and death-inducing ligands, making them important in cell survival and death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the MMPs. Synthetic inhibitors have been developed for the treatment of arthritis and cancer. These hydroxymate-based compounds have been shown to reduce injury in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), cerebral ischemia, intracerebral hemorrhage, and viral and bacterial infections. MPs have both beneficial and detrimental roles; understanding their expression in various CNS insults will allow for the use of MMP inhibitors in the treatment of neurological disorders. GLIA 39: 279 -291, 2002.

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Section: Cellular Localization Of the Mmps In Brainmentioning

confidence: 94%

Section: Studies Of Mmps In Brain Cell Culturesmentioning

confidence: 99%

Section: Cellular Localization Of the Mmps In Brainmentioning

confidence: 99%

Section: Endogenous Mmp Inhibitors: Tissue Inhibitors Of Metalloprotementioning

confidence: 99%

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Matrix metalloproteinases in neuroinflammation

Rosenberg

2002

Glia

Self Cite

778

667

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“…During the inflammatory response after cerebral ischemia, gelatinase A (MMP-2) and gelatinase B (MMP-9) are highly upregulated in different cell types in the central nervous system, including endothelial cells, microglia, astrocytes, and neurons (Asahi et al, 2000;Rosenberg et al, 2001;Rivera et al, 2002;Magnoni et al, 2004). In addition, circulating neutrophils are also a source of MMPs (Justicia et al, 2003;Gidday et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Near-Infrared Fluorescence Imaging of Matrix Metalloproteinase Activity after Cerebral Ischemia

Klohs

Baeva

Steinbrink

et al. 2009

J Cereb Blood Flow Metab

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Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of cerebral ischemia. In this study, we explored whether MMP activity can be visualized by noninvasive nearinfrared fluorescence (NIRF) imaging using an MMP-activatable probe in a mouse model of stroke. C57Bl6 mice were subjected to transient middle cerebral artery occlusion (MCAO) or sham operation. Noninvasive NIRF imaging was performed 24 h after probe injection, and target-tobackground ratios (TBRs) between the two hemispheres were determined. TBRs were significantly higher in MCAO mice injected with the MMP-activatable probe than in sham-operated mice and in MCAO mice that were injected with the nonactivatable probe as controls. Treatment with an MMP inhibitor resulted in significantly lower TBRs and lesion volumes compared to injection of vehicle. To test the contribution of MMP-9 to the fluorescence signal, MMP9-deficient (MMP9 À/À ) mice and wild-type controls were subjected to MCAO of different durations to attain comparable lesion volumes. TBRs were significantly lower in MMP9 À/À mice, suggesting a substantial contribution of MMP-9 activity to the signal. Our study shows that MMP activity after cerebral ischemia can be imaged noninvasively with NIRF using an MMP-activatable probe, which might be a useful tool to study MMP activity in the pathophysiology of the disease.

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Metalloproteinases and the Brain Microvasculature

Krause

Lohmann

2006

Blood‐Brain Barriers

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Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures

Cited by 360 publications

References 19 publications

Matrix metalloproteinases in neuroinflammation

Matrix metalloproteinases in neuroinflammation

In Vivo Near-Infrared Fluorescence Imaging of Matrix Metalloproteinase Activity after Cerebral Ischemia

Metalloproteinases and the Brain Microvasculature

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