Matrix Metalloproteinase-9 Levels are Associated with Brain Lesion and Persistent Venous Occlusion in Patients with Cerebral Venous Thrombosis

Abstract Background Elucidating mechanisms of brain damage in cerebral venous thrombosis (CVT) would be instrumental to develop targeted therapies and improve prognosis prediction. Matrix metalloproteinase-9 (MMP-9), a gelatinase that degrades major components of the basal lamina, has been associated to blood–brain barrier disruption. We aimed to assess, in patients with CVT, the temporal change in serum concentrations of MMP-9 and its association with key imaging and clinical outcomes. Methods Pathophysiology of Venous Infarction—PRediction of InfarctiOn and RecanalIzaTion in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Serial collection of peripheral blood samples performed on day 1, 3, and 8, and standardized magnetic resonance imaging on day 1, 8, and 90. MMP-9 was quantified using enzyme-linked immunosorbent assay in 59 patients and 22 healthy controls. Primary outcomes were parenchymal brain lesion, early evolution of brain lesion, early recanalization, and functional outcome on day 90. Results CVT patients with parenchymal brain lesion had higher baseline concentrations of MMP-9 compared with controls (adjusted p = 0.001). The area under receiver operating characteristic curve value for MMP-9 for predicting brain lesion was 0.71 (95% confidence interval [CI]: 0.57–0.85, p = 0.009). Patients with venous recanalization showed early decline of circulating MMP-9 and significantly lower levels on day 8 (p = 0.021). Higher MMP-9 on day 8 was associated with persistent venous occlusion (odds ratio: 1.20 [per 20 ng/mL], 95% CI: 1.02–1.43, p = 0.030). Conclusion We report a novel relationship among MMP-9, parenchymal brain damage, and early venous recanalization, suggesting that circulating MMP-9 is a dynamic marker of brain tissue damage in patients with CVT.

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Binding of Pro-Matrix Metalloproteinase 9 by Fusobacterium nucleatum subsp. nucleatum as a Mechanism To Promote the Invasion of a Reconstituted Basement Membrane

Infection and Immunity ◽

10.1128/iai.72.10.6160-6163.2004 ◽

2004 ◽

Vol 72 (10) ◽

pp. 6160-6163 ◽

Cited By ~ 9

Author(s):

Renée Gendron ◽

Pascale Plamondon ◽

Daniel Grenier

Keyword(s):

Basement Membrane ◽

Matrix Metalloproteinase ◽

Colorimetric Assay ◽

Active Form ◽

Fusobacterium Nucleatum ◽

Matrix Metalloproteinase 9 ◽

Enzyme Linked Immunosorbent Assay ◽

Potential Contribution ◽

Invasive Potential ◽

Metalloproteinase 9

ABSTRACT In this study, we investigated the ability of Fusobacterium nucleatum subsp. nucleatum to increase its tissue-invasive potential by acquiring cell-associated human matrix metalloproteinase 9 (MMP-9) activity. Binding of pro-MMP-9 to fusobacteria was demonstrated by enzyme-linked immunosorbent assay. Zymography and a colorimetric assay showed that bound pro-MMP-9 can be converted into a proteolytically active form. The potential contribution of this acquired host activity in tissue invasion was demonstrated using a reconstituted basement membrane (Matrigel).

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Progesterone attenuates cerebral edema in neonatal rats with hypoxic-ischemic brain damage by inhibiting the expression of matrix metalloproteinase-9 and aquaporin-4

Experimental and Therapeutic Medicine ◽

10.3892/etm.2013.1116 ◽

2013 ◽

Vol 6 (1) ◽

pp. 263-267 ◽

Cited By ~ 24

Author(s):

XIAOYIN WANG ◽

JUNHE ZHANG ◽

YUXIN YANG ◽

WEIHUA DONG ◽

FANG WANG ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Brain Damage ◽

Cerebral Edema ◽

Matrix Metalloproteinase 9 ◽

Aquaporin 4 ◽

Neonatal Rats ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Metalloproteinase 9

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Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis

Multiple Sclerosis Journal ◽

10.1191/1352458502ms800oa ◽

2002 ◽

Vol 8 (3) ◽

pp. 222-228 ◽

Cited By ~ 74

Author(s):

G M Liuzzi ◽

M Trojano ◽

M Fanelli ◽

C Avolio ◽

A Fasano ◽

...

Keyword(s):

Multiple Sclerosis ◽

Matrix Metalloproteinase ◽

Neurological Diseases ◽

Inverse Correlation ◽

Serum Levels ◽

Matrix Metalloproteinase 9 ◽

Enzyme Linked Immunosorbent Assay ◽

Intrathecal Synthesis ◽

Healthy Donors ◽

Metalloproteinase 9

Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF) samples from patients with neurological diseases. Patients with relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels comparable to those from patients with inflammatory neurological diseases (INDs), but higher than patients with non-inflammatory neurological diseases (NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison with inactive RR-MS implying that MMP-9 in MS is related with clinical disease activity. A correlation between the CSF/serum albumin (QAlb) and CSF/serum MMP-9 (QMMP-9) was observed in IND and NIND but not in RR-MS patients, indicating that CSF MMP-9 levels in NIND and IND patients could be influenced by serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients had higher values of QMMP-9:QAlb (MMP-9 index) than IND and NIND patients suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal synthesis of MMP-9. A significant inverse correlation was found between MMP-9 and its endogenous inhibitor TIMP-1 in RR-MS indicating that in MS patients both the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute to BBB disruption and T-lymphocyte entry into the CNS.

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Urinary Matrix Metalloproteinase-9 and Nephrin in Idiopathic Membranous Nephropathy: A Cross-Sectional Study

Disease Markers ◽

10.1155/2021/1620545 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Akankwasa Gilbert ◽

An Changjuan ◽

Cheng Guixue ◽

Liu Jianhua ◽

Qin Xiaosong

Keyword(s):

Matrix Metalloproteinase ◽

Membranous Nephropathy ◽

Healthy Subjects ◽

Kidney Injury ◽

Matrix Metalloproteinase 9 ◽

Idiopathic Membranous Nephropathy ◽

Enzyme Linked Immunosorbent Assay ◽

Cross Sectional ◽

Glomerular Diseases ◽

Metalloproteinase 9

Aim. Idiopathic membranous nephropathy (IMN) has a varied clinical course that requires accurate prediction as a prerequisite for treatment administration. Currently, its prognosis relies on proteinuria, a clinical parameter whose onset lags behind kidney injury. Increased urinary excretion of matrix metalloproteinase-9 (MMP-9) and nephrin has been reported in a number of IMN-like glomerular diseases in which they reflected disease severity. However, little or nothing is known of the importance of these biomarkers in IMN, a major cause of adult nephrotic syndrome. To highlight their potential, we measured both biomarkers and assessed their relationships with key parameters of renal function in IMN. Methods. We quantified urinary MMP-9 and nephrin in 107 biopsy-proven IMN patients and 70 healthy subjects by enzyme-linked immunosorbent assay (ELISA). We then compared biomarker levels between patients and healthy subjects and among patients with different clinical features. We also determined the relationship of each biomarker with proteinuria and the estimated glomerular filtration rate (eGFR). Results. Urinary MMP-9 and nephrin were significantly higher in IMN compared to healthy controls. Unlike nephrin, MMP-9 correlated significantly with proteinuria and was significantly higher among patients with nephrotic range proteinuria. Both biomarkers were correlated with eGFR, but only MMP-9 was significantly higher in patients with eGFR less than 90 ml/min/1.73 m2. Conclusion. Our findings suggest that urinary MMP-9 holds a greater potential than urinary nephrin in monitoring the severity of IMN.

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PECULIARITIES OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND MATRIX METALLOPROTEINASE-9 EXPRESSION DYNAMICS IN PATIENTS WITH PARANOID SCHIZOPHRENIA DEPENDING ON THE DURATION OF THE DISEASE

Wiadomości Lekarskie ◽

10.36740/wlek202111108 ◽

2021 ◽

Vol 74 (11) ◽

pp. 2728-2732

Author(s):

Ivan R. Romash ◽

Mykhailo I. Vynnyk

Keyword(s):

Matrix Metalloproteinase ◽

Blood Serum ◽

Neurotrophic Factor ◽

Paranoid Schizophrenia ◽

Serum Levels ◽

Brain Derived Neurotrophic Factor ◽

Matrix Metalloproteinase 9 ◽

Enzyme Linked Immunosorbent Assay ◽

Group I ◽

Metalloproteinase 9

The aim: To study the expression of brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in the blood serum of patients with paranoid schizophrenia and to trace the features of their dynamics depending on the duration of the disease and analyse the correlation between BDNF, MMP-9 serum levels and symptoms severity by using the Positive and Negative Syndrome Scale (PANSS). Materials and methods: The study included 120 patients, namely 20 patients with paranoid schizophrenia diagnosed less than 3 years ago (Сomparison Group) and 100 patients with a diagnosis of paranoid schizophrenia (Study Group): 20 of them have been suffering from this disease from 3 to 5 years (Subgroup I); 10 patients – from 5 to 10 years (Subgroup II); 10 patients – from 10 to 15 years (Subgroup III); 10 patients – from 15 to 20 years (Subgroup IV); 10 patients – from 25 years and more (Subgroup V). The groups did not differ with respect to age or gender. The content of BDNF and MMP-9 in blood serum was determined by enzyme-linked immunosorbent assay. Results: BDNF concentration averaged 28.327 ± 5.32 pg/ml in the patients of Group I; 25.40 ± 2.31 pg/ml in Group II; 24.32 ± 3.1 pg/ml in Group III; 23.8 ± 1.32 pg/ml in Group IV; 21.39 ± 0.97 pg/ml in Group V; 9.36 ± 4.38 pg/ml in Group VI. The expression of MMP-9 in the experimental groups constituted: 942.84 ± 87.80 pg/ml, 1042.84 ± 87.80 pg/ml, 1142.53 ± 77.20 pg/ml, 1752.84 ± 77.80 pg/ml, 1542.84 ± 37.70 pg/ml, 2042.74 ± 47.80 pg/ml, respectively. Decreased BDNF negatively correlated with MMP-9 expression (r=0.46; p<0.05). Conclusions: The development of paranoid schizophrenia was manifested by an imbalance in BDNF level and MMP-9 expression which could affect neurogenesis, synapticplasticity, ability to learn and remember, therefore, they could be considered as diagnostic markers of the pathology. With the increase in the duration of the studied pathology, BDNF parameters decreased and MMP-9 expression increased. A negative correlation between them was noted.

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Interrupted intracarotid artery cold saline infusion as an alternative method for neuroprotection after ischemic stroke

Neurosurgical FOCUS ◽

10.3171/2012.5.focus1215 ◽

2012 ◽

Vol 33 (1) ◽

pp. E10 ◽

Cited By ~ 19

Author(s):

Ya-Bin Ji ◽

Yong-Ming Wu ◽

Zhong Ji ◽

Wei Song ◽

Sui-Yi Xu ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Traditional Method ◽

Neuron Specific Enolase ◽

Matrix Metalloproteinase 9 ◽

Saline Infusion ◽

Neurological Deficits ◽

Enzyme Linked Immunosorbent Assay ◽

Cold Saline ◽

Metalloproteinase 9 ◽

Brain Water

Object Intracarotid artery cold saline infusion (ICSI) is an effective method for protecting brain tissue, but its use is limited because of undesirable secondary effects, such as severe decreases in hematocrit levels, as well as its relatively brief duration. In this study, the authors describe and investigate the effects of a novel ICSI pattern (interrupted ICSI) relative to the traditional method (uninterrupted ICSI). Methods Ischemic strokes were induced in 85 male Sprague-Dawley rats by occluding the middle cerebral artery for 3 hours using an intraluminal filament. Uninterrupted infusion groups received an infusion at 15 ml/hour for 30 minutes continuously. The same infusion speed was used in the interrupted infusion groups, but the whole duration was divided into trisections, and there was a 20-minute interval without infusion between sections. Forty-eight hours after reperfusion, H & E and silver nitrate staining were utilized for morphological assessment. Infarct sizes and brain water contents were determined using H & E staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100β protein, and matrix metalloproteinase 9 (MMP-9) in the serum were determined using enzyme-linked immunosorbent assay. Neurological deficits were also evaluated. Results Histology showed that interrupted ICSI did not affect neurons or fibers in rat brains, which suggests that this method is safe for brain tissues with ischemia. The duration of hypothermia induced by interrupted ICSI was longer than that induced via the traditional method, and the decrease in hematocrit levels was less pronounced. There were no differences in infarct size or brain water content between uninterrupted and interrupted ICSI groups, but neuron-specific enolase and matrix metalloproteinase 9 serum levels were more reduced after interrupted ICSI than after the traditional method. Conclusions Interrupted ICSI is a safe method. Compared with traditional ICSI, the interrupted method has a longer duration of hypothermia and less effect on hematocrit and offers more potentially improved neuroprotection, thereby making it more attractive as an infusion technique in the clinic.

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Increased matrix metalloproteinase-9 in male elderly with low 25-hydroxy-vitamin D

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2016.v35.171-180 ◽

2016 ◽

Vol 35 (3) ◽

pp. 171

Author(s):

Pusparini Pusparini ◽

Lie Tanu Merijanti ◽

Novia I. Sudharma

Keyword(s):

Vitamin D ◽

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Enzyme Linked Immunosorbent Assay ◽

Chi Square ◽

Cross Sectional ◽

25 Hydroxy Vitamin D ◽

Male Subjects ◽

Metalloproteinase 9 ◽

Female Subjects

Background One of the extra-skeletal roles of vitamin D for health is associated with cardiovascular disease. Poor vitamin D status has been associated with vascular endothelial dysfunction. There were controversial results about the association between vitamin D deficiency and matrix metalloproteinase 9 (MMP-9) concentration. The purpose of the present study was to determine the concentrations of 25(OH) vitamin D [25(OH)D] in an elderly population and to find any association between 25(OH)D and MMP-9 concentrations.Methods This study was of cross-sectional design involving 160 male and female subjects aged 55–65 years, in South Jakarta, Indonesia. Determination of MMP-9 and 25(OH)D concentrations was done concurrently on subjects who met the inclusion and exclusion criteria after all study subjects had been selected. 25(OH)D and MMP-9 concentrations were assessed by direct competitive chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) respectively. Statistical analysis used chi square and t tests.Results Mean 25(OH)D concentration in the study subjects was 14.4 ± 6.4 ng/mL. A total of 68.8% of subjects had a 25(OH)D level of <20 ng/mL, and 31.2 % had a 25(OH)D level of >20 ng/mL.There was an increased MMP-9 concentration in male subjects with a 25(OH)D level of <20 ng/mL compared with subjects with 25(OH)D level of >20 ng/mL (p=0.011), but not among female subjects (p=0.809).Conclusion The MMP-9 concentration was increased among male subjects with low level of (OH)D. This study confirmed that 25(OH)D concentration may have a potential role in endothelial function.

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