Matrix Metalloproteinase 9 Inhibition Reduces Early Brain Injury in Cortex After Subarachnoid Hemorrhage

2011 ◽  
pp. 81-84 ◽  
Author(s):  
Zong-duo Guo ◽  
Xiao-dong Zhang ◽  
Hai-tao Wu ◽  
Bin Lin ◽  
Xiao-chuan Sun ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Matrix Metalloproteinase ◽  
Early Brain Injury ◽  
Matrix Metalloproteinase 9 ◽  
Metalloproteinase 9

Matrix metalloproteinase-9 potentiates early brain injury after subarachnoid hemorrhage

2010 ◽  
Vol 32 (7) ◽  
pp. 715-720 ◽  
Author(s):  
Zongduo Guo ◽  
Xiaochuan Sun ◽  
Zhaohui He ◽  
Yong Jiang ◽  
Xiaodong Zhang ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Matrix Metalloproteinase ◽  
Early Brain Injury ◽  
Matrix Metalloproteinase 9 ◽  
Metalloproteinase 9

Abstract WP288: Inter-Alpha Inhibitor Proteins Reduce the Presence of Neutrophils and Matrix Metalloproteinase-9 Positive Neutrophils in Damaged Brain Regions of Neonates with Hypoxic-Ischemic (HI) Brain Injury

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Adriel Barrios-Anderson ◽  
Xiaodi Chen ◽  
Yow-Pin Lim ◽  
Barbara S Stonestreet
Keyword(s):  
Brain Injury ◽  
Corpus Callosum ◽  
Matrix Metalloproteinase ◽  
Right Hemisphere ◽  
Brain Regions ◽  
Matrix Metalloproteinase 9 ◽  
Male Rats ◽  
Control Group ◽  
Neonatal Rats ◽  
Metalloproteinase 9

Introduction: Inter-alpha inhibitor proteins (IAIPs) are immunomodulatory proteins that play a significant anti-inflammatory role in hypoxic ischemic (HI) brain injury. We have shown that administering IAIPs after HI improves histopathological brain injury, brain weight, and behavioral outcomes in neonatal rats. Neutrophils are specialized leukocytes known to infiltrate the brain parenchyma and exacerbate neuronal injury after HI. One molecular mechanism by which neutrophils exert damage on the blood-brain barrier (BBB) and brain tissue after ischemia is by the release of matrix metalloproteinase-9 (MMP9), an enzyme that breaks down the extracellular matrices of surrounding cells. Objective: To determine the effect of IAIPs on neutrophil infiltration and release of MMP9 in neonatal rats after HI. Methods: The Vannucci model was used to induce neonatal HI in postnatal day 7 rats that were assigned to a Non-ischemic sham-control group (Sham, n=12), right-sided carotid ligation with exposure to hypoxia (8% oxygen for 90 min) treated with placebo group (PL-HI, n=17), or an IAIP treated group (IAIP-HI, n=17). Rat sex was recorded. IAIP (30 mg/kg) or PL was given intraperitoneally at 0, 24 and 48 h after HI. We removed the rat brain after 72h and performed immunohistochemistry using MPO (neutrophil selective) and MMP9 fluorescent markers. We performed stereological analyses with the StereoInvestigator 10.0 Fractionator probe without knowledge of group assignment to quantify neutrophils and MMP9 positive cells present within the right hemisphere, cortex, corpus callosum, and hippocampus. Results: MPO positive cells were significantly reduced in male IAIP treated rats compared with PL-HI in the overall damaged hemisphere (p<0.01) and the corpus callosum (p<0.05). Further, we observed MPO and MMP9 co-localization, and IAIP treatment reduced the presence of MMP9 positive neutrophils in the cortex of male rats compared to placebo (P<0.05).

379 Matrix Metalloproteinase-9: A Key Contributor to Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 290-290
Author(s):  
Ananth K Vellimana ◽  
Meng-Liang Zhou ◽  
Itender Singh ◽  
Diane J Aum ◽  
James Nelson ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Matrix Metalloproteinase ◽  
Delayed Cerebral Ischemia ◽  
Experimental Models ◽  
Matrix Metalloproteinase 9 ◽  
Multiple Components ◽  
Neurobehavioral Deficits ◽  
Metalloproteinase 9 ◽  
Expression And Activity

Abstract INTRODUCTION Delayed cerebral ischemia (DCI) is an independent risk factor for poor outcome after subarachnoid hemorrhage (SAH) and is multi-factorial in etiology. A few prior studies have suggested a key role for matrix metalloproteinase-9 (MMP-9) in the pathogenesis of early brain injury (EBI) after SAH. In contrast, the role of MMP-9 in DCI is poorly understood. In this study, we examined the contribution of MMP-9 to DCI after SAH. METHODS Wild type (WT) and MMP-9-/− mice were subjected to sham or endovascular perforation SAH surgery. Daily neurobehavioral assessments were performed, and vasospasm was assessed on post-SAH Day 3. MMP-9 expression and activity were also assessed. In separate experiments, WT mice or MMP-9-/− were administrated vehicle or Minocycline and subjected to vasospasm, neurobehavioral, and microthrombi assessments. In another experiment, male New Zealand White rabbits were subjected to sham surgery or cisterna magna injection SAH, and administered vehicle or Minocycline, followed by vasospasm assessment on post-SAH day 3. RESULTS >SAH resulted in a significant increase in MMP-9 expression and activity. Genetic inhibition of MMP-9 (MMP-9-/− mice) and pharmacological inhibition of MMP-9 (pre-SAH Minocycline administration) resulted in significantly decreased vasospasm and neurobehavioral deficits after SAH. Post-SAH administration of Minocycline resulted in significant attenuation of multiple components of DCI including vasospasm, microthrombosis and neurobehavioral deficits. Consistent with experiments in mice both pre- and post-SAH administration of Minocycline attenuated vasospasm in rabbits. CONCLUSION Our study provides definitive mechanistic evidence that MMP-9 is a key player in the pathogenesis of DCI after SAH. We observed consistent attenuation of SAH-induced neurovascular deficits with both pre- and post-SAH administration of minocycline across different species and experimental models of SAH, and against multiple components of DCI. The excellent safety profile of minocycline in humans and promising results in experimental SAH studies suggest that a clinical trial in SAH patients is warranted.

scholarly journals Matrix metalloproteinase-9 gene polymorphisms and their interaction with environment on subarachnoid hemorrhage risk

2018 ◽  
Vol 243 (9) ◽  
pp. 749-753 ◽  
Author(s):  
Tao Wang ◽  
Wanxing Fu ◽  
Shuang Song ◽  
Yanlong Han ◽  
Lihong Yao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Single Nucleotide Polymorphisms ◽  
Matrix Metalloproteinase ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Matrix Metalloproteinase 9 ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hemorrhage Risk ◽  
Metalloproteinase 9

The current study aimed to investigate the relations of three single nucleotide polymorphisms of matrix metalloproteinase-9 gene, and single nucleotide polymorphisms-smoking interaction to subarachnoid hemorrhage risk. The optimal pattern of the interaction among single nucleotide polymorphisms and smoking was selected by generalized multifactor dimensionality reduction. The association between the three single nucleotide polymorphisms within the matrix metalloproteinase-9 gene was analyzed by logistic regression test. As well as genetic risk of subarachnoid hemorrhage interactions with smoking, the risk of subarachnoid hemorrhage in carriers with the rs3918242 (T) was significantly higher than in carriers carrying CC (genotype: CT + TT vs. CC), adjusted OR (95% CI) = 1.58 (1.25–2.03), and in carriers carrying rs17576- (genotype: AG + GG vs. AA), adjust OR (95% CI) = 1.62 (1.19–2.13). However, after adjusting for covariates, we did not find any direct association between rs17577 and subarachnoid hemorrhage risk. The generalized multifactor dimensionality reduction model shows a potential relation between rs3918242 and smoking risk for subarachnoid hemorrhage ( P = 0.0010). After covariates adjustment, current smokers with rs3918242-CT or TT genotype, compared to never-smokers with rs3918242-CC genotype, OR (95% CI) = 2.57 (1.74–3.46), have a higher subarachnoid hemorrhage risk. Our study showed that the rs3918242 (T) and rs17576 (G), the cross reaction between rs3918242 and smoking increased the risk of subarachnoid hemorrhage. Impact statement Matrix metalloproteinase-9 ( MMP-9) is a possible candidate gene for some diseases, including metabolic syndrome, stroke, coronary artery disease (CAD). But to date, limited data focused on the relationship between MMP-9 gene SNPs and SAH susceptibility. The purpose of this study was to evaluate SNPs of MMP-9 gene and their interaction with environmental factors with SAH risk based on a Chinese population.

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