Proteolytic activity during cortical development is distinct from that involved in hypoxic ischemic injury

Ranasinghe, H.; Williams, Chris; Christophidis, Larissa Joy; Mitchell, Murray D.; Fraser, Mhoyra; Scheepens, Arjan

doi:10.1016/j.neuroscience.2008.07.069

Cited by 25 publications

(25 citation statements)

References 50 publications

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“…This is the first demonstration that in mixed glial cultures MMP-2 activity is altered by LPS but not TNF-α and suggests that while cytokines produced by LPS exposure are likely to play a role in MMP-2 activation in the short term, it is unlikely to be facilitated by TNF-α alone. With regard to MMP-9, in vivo studies have shown an up-regulation within the acute period after injury [41,42], however, our results show an increase over the long term only, suggesting that in vivo it is not glia producing MMP-9 immediately following injury but likely a neuronal or peripheral central nervous system-invading source.…”

Section: Discussioncontrasting

confidence: 75%

Inhibition of Matrix Metalloproteinases-2/-9 Transiently Reduces Pre-Oligodendrocyte Loss during Lipopolysaccharide- but Not Tumour Necrosis Factor-alpha-Induced Inflammation in Fetal Ovine Glial Culture

Weaver-Mikaere¹,

Gunn

Mitchell³

et al. 2013

Dev Neurosci

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To determine whether increased matrix metalloproteinase (MMP) proteolytic activity plays a pathological role in infection/inflammation-induced preterm brain injury, primary cultures of preterm (day 90 of gestation; term 145 days) fetal ovine mixed glia were exposed to 24-96 h of lipopolysaccharide (LPS, 1 μg/ml) or tumour necrosis factor-α (TNF-α, 100 ng/ml). MMP-2 mRNA levels were significantly increased after TNF-α (96 h) and LPS exposure (48 and 96 h), and MMP-9 mRNA levels were significantly increased at 48 and 96 h after TNF-α. On zymography, the active form of secreted MMP-2 was significantly increased 24 h after LPS, but not TNF-α. Both active and latent forms of MMP-9 gelatinolytic activity were significantly increased by TNF-α (96 h) and LPS (72 and 96 h). On reverse zymography, inhibitory activity of TIMP-1 but not TIMP-2 was significantly increased by TNF-α and LPS. SB-3CT-mediated MMP-2 and MMP-9 inhibition transiently reduced LPS-induced oligodendrocyte cell death but had no effect during TNF-α exposure. Collectively, these observations suggest a limited, transient effect of MMPs on immature white matter damage associated with infection but not TNF-α-mediated inflammation.

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Section: Discussioncontrasting

confidence: 75%

Inhibition of Matrix Metalloproteinases-2/-9 Transiently Reduces Pre-Oligodendrocyte Loss during Lipopolysaccharide- but Not Tumour Necrosis Factor-alpha-Induced Inflammation in Fetal Ovine Glial Culture

Weaver-Mikaere¹,

Gunn

Mitchell³

et al. 2013

Dev Neurosci

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“…Diseases of the nervous system. In the nervous system, relatively high mRNA and protein levels of MMP-14, MMP-15, and MMP-24 and TIMP-1 and TIMP-3 are found in the perinatal rodent central nervous system (CNS) but generally decline with age (Ayoub et al, 2005;Fager and Jaworski, 2000;Jaworski, 2000;Ranasinghe et al, 2009;Rivera et al, 1997;Ulrich et al, 2005;Vaillant et al, 1999).…”

Section: Tumorigenesismentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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“…Alternatively, blood-brain barrier breakdown and the inflammatory response, involved early in focal injury, could lead to an increase not only in MMP-9 but also in MMP-2, MMP-3, and TIMP-3. However, reports regarding MMP-2 are often contradictory (4,22,25,26), and we therefore preferred to focus on the more reliable marker, MMP-9 (9). The second peak of MMP-9 in the brain might also reflect the secondary phase of energy failure induced by HI (27).…”

Section: Mmp-9/timp-1 In Perinatal Brain Injurymentioning

confidence: 99%

“…Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in multiple processes during development and in adulthood (3)(4)(5), including perinatal hypoxia-ischemia (HI) and white matter damage in human neonates. Recent studies in adult MMP-9 knockout mice have demonstrated the key role played by this metalloproteinase in the pathophysiology of traumatic and hypoxic-ischemic (HI) brain injury (6).…”

mentioning

confidence: 99%

Increased MMP-9 and TIMP-1 in mouse neonatal brain and plasma and in human neonatal plasma after hypoxia–ischemia: a potential marker of neonatal encephalopathy

et al. 2011

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ArticlesTranslational Investigation nature publishing group INTRODUCTION:To implement neuroprotective strategies in newborns, sensitive and specific biomarkers are needed for identifying those who are at risk for brain damage. We evaluated the effectiveness of matrix metalloproteinases (MMPs) and their naturally occurring tissue inhibitors of metalloproteinases (TIMPs) in predicting neonatal encephalopathy (Ne) damage in newborns. RESULTS: Plasma MMP-9 and TIMP-1 levels were upregulated as early as 1 h after the hI insult but not did not show such elevations after other types of injury (ibotenate-induced excitotoxicity, hypoxia, lipopolysaccharide-induced inflammation), and brain levels reflected this increase soon thereafter. We confirmed these results by carrying out plasma MMP-9 and TIMP-1 measurements in human newborns with Ne. In these infants, protein levels of MMP-9 and TIMP-1 were found to be elevated during a short window up to 6 h after birth. DISCUSSION: This feature is particularly useful in identifying newborns in need of neuroprotection. a second peak observed 72 h after birth is possibly related to the second phase of energy failure after a hI insult. Our data, although preliminary, support the use of MMP-9 and TIMP-1 as early biomarkers for the presence and extent of perinatal brain injury in human term newborns. METHODS: We first used a mouse model of neonatal hI injury to explore mechanistic aspects such as the time course of these markers after the hypoxia-ischemia event, and the correlation between the levels of these candidate markers in brain and plasma.T he major perinatal brain lesions associated with cerebral palsy and cognitive impairment are periventricular white matter damage and cortical-subcortical lesions, observed mainly in preterm and term infants, respectively (1,2). A crucial step for the implementation of neuroprotective therapies is the rapid detection of neonates at risk. Despite this urgent need, no appropriate and easily detectable biomarkers for perinatal injury are currently available.Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in multiple processes during development and in adulthood (3-5), including perinatal hypoxia-ischemia (HI) and white matter damage in human neonates. Recent studies in adult MMP-9 knockout mice have demonstrated the key role played by this metalloproteinase in the pathophysiology of traumatic and hypoxic-ischemic (HI) brain injury (6). Concordantly, MMP-9 has been shown to have deleterious effects in the immature brain after HI injury (7). Several of these studies demonstrated a significant increase in MMP-9 expression in the central nervous system within the first 24 h after the insult. MMP-9 also has long-term beneficial effects on neurovascular remodeling and behavioral recovery after stroke in adult rats (8,9). In the adult rat central nervous system, elevated TIMP-1 expression levels may play a neuroprotective role after kainate-induced excitotoxic seizures (10), and gene transfer of TIMP-...

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Proteolytic activity during cortical development is distinct from that involved in hypoxic ischemic injury

Cited by 25 publications

References 50 publications

Inhibition of Matrix Metalloproteinases-2/-9 Transiently Reduces Pre-Oligodendrocyte Loss during Lipopolysaccharide- but Not Tumour Necrosis Factor-alpha-Induced Inflammation in Fetal Ovine Glial Culture

Inhibition of Matrix Metalloproteinases-2/-9 Transiently Reduces Pre-Oligodendrocyte Loss during Lipopolysaccharide- but Not Tumour Necrosis Factor-alpha-Induced Inflammation in Fetal Ovine Glial Culture

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Increased MMP-9 and TIMP-1 in mouse neonatal brain and plasma and in human neonatal plasma after hypoxia–ischemia: a potential marker of neonatal encephalopathy

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