The increased activation of matrix metalloproteinase 2/9 and gradual degradation of claudin in rat models of middle cerebral artery ischemia

doi:10.3969/j.issn.2095-4344.2015.27.011

Abstract

Abstract:

BACKGROUND: During the process of acute brain injury after stroke, matrix metalloproteinase can undermine the integrity of vascular basement membrane, promote the migration of neutrophils and inflammatory factors, and cause secondary brain injury.
OBJECTIVE: To investigate the activation of matrix metalloproteinase 2/9 and the degradation rule of claudin in rat models of middle cerebral artery ischemia at different ischemic durations.
METHODS: Thirty-nine male SD rats were randomly divided into three groups according to different ischemic
durations (3, 5 and 7 hours) . Middle cerebral artery occlusion (stroke) model was established using modified suture method, i.e., separation of the external carotid artery, inserting the suture into the internal carotid artery through the external carotid artery, and eventually reaching the middle cerebral artery. The ischemic duration in these three groups was respectively 3 , 5 and 7 hours. After 2 hours of reperfusion, Zea-Longa score and Ludmila Belayev score, brain infarct area, matrix metalloproteinase 2/9 activities and claudin 5 degradation were determined in each group.
RESULTS AND CONCLUSION: With the extension of ischemic duration, brain infarct area gradually increased, central nervous system damage gradually aggravated, matrix metalloproteinase 2/9 activities gradually increased, and claudin-5 expression gradually decreased. There were significant differences between any two ischemic durations in terms of each of above-mentioned indices. The results indicate that after long duration of ischemia, the progressive damage of brain tissue can cause the gradual increase of activation of matrix metalloproteinase 2/9 and the gradual degradation of claudin 5.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

Key words: Cerebral Ischemia, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Claudin

CLC Number:

R318

Liang Jia,Qi Zhi-feng, Shi Wen-juan, Liu Ke-jian. The increased activation of matrix metalloproteinase 2/9 and gradual degradation of claudin in rat models of middle cerebral artery ischemia [J]. Chinese Journal of Tissue Engineering Research, 2015, 19(27): 4322-4327.

Figures/Tables 3

References

[1] Banerjee P,Jana S,Chakraborty S,et al.Inflammation and MMPs in alcohol-induced liver diseases and protective action of antioxidants.Indian J Biochem Biophys.2013; 50(5): 377-386.

[2] Cavdar Z,Ozbal S,Celik A,et al.The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model. Biotech Histochem.2014; 89(4):304-314.

[3] Tang X,Zhong W,Tu Q,et al.NADPH oxidase mediates the expression of MMP-9 in cerebral tissue after ischemia- reperfusion damage.Neurol Res.2014;36(2):118-125.

[4] Li M,Ma RN,Li LH,et al.Astragaloside IV reduces cerebral edemapost-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4. Eur J Pharmacol. 2013;715(1-3): 189-195.

[5] Cao J,Geng L,Wu Q,et al. Spatiotemporal expression of matrix metalloproteinases (MMPs) is regulated by the Ca2+-signal transducer S100A4 in the pathogenesis of thoracic aortic aneurysm.PLoS One.2013;8(7):e70057.

[6] Moniche F,Montaner J,Gonzalez-Marcos JR,et al.Intra-arterial bone marrow mononuclear cell transplantation correlates with GM-CSF, PDGF-BB, and MMP-2 serum levels in stroke patients: results from a clinical trial. Cell Transplant.2014;23 Suppl 1:S57-S64.

[7] Bai X,Zhang X,Chen L,et al. Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-kappaB, MMP-9 and up-regulated claudin-5 expression. Neurochem Res.2014;39(8):1405-1415.

[8] Sapojnikova N,Kartvelishvili T,Asatiani N,et al.Correlation between MMP-9 and extracellular cytokine HMGB1 in prediction of human ischemic stroke outcome. Biochim Biophys Acta.2014;1842(9):1379-1384.

[9] Tsuji K,Aoki T,Tejima E,et al.Tissue plasminogen activator promotes matrix metalloproteinase-9 upregulation after focal cerebral ischemia.Stroke.2005; 36(9):1954-1959.

[10] Zhao H,Wang R,Wu X,et al.Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion. J Neuroimmune Pharmacol. 2015;10(1): 153-161.

[11] Wang R, Wu X, Liang J et al.Intra-artery infusion of recombinant human erythropoietin reduces blood-brain barrier disruption in rats following cerebral ischemia and reperfusion.Int J Neurosci.2014.[Epub ahead of print]

[12] Won S,Lee JH,Wali B,et al.Progesterone attenuates hemorrhagic transformation after delayed tPA treatment in an experimental model of stroke in rats: involvement of the VEGF-MMP pathway.J Cereb Blood Flow Metab.2014;34(1): 72-80.

[13] Wang L,Li Z,Zhang X,et al.Protective effect of shikonin in experimental ischemic stroke: attenuated TLR4, p-p38MAPK, NF-kappaB, TNF-alpha and MMP-9 expression, up-regulated claudin-5 expression, ameliorated BBB permeability. Neurochem Res.2014; 39(1):97-106.

[14] Dong W, Qi Z, Liang J,et al.Reduction of zinc accumulation in mitochondria contributes to decreased cerebral ischemic injury by normobaric hyperoxia treatment in an experimental stroke model.Exp Neurol.2015.[Epub ahead of print]

[15] Marinescu M,Bouley J,Chueh J,et al.Clot injection technique affects thrombolytic efficacy in a rat embolic stroke model: implications for translaboratory collaborations. J Cereb Blood Flow Metab.2014;34(4):677-682.

[16] Bai X,Zhang X,Chen L,et al.Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-kappaB, MMP-9 and up-regulated claudin-5 expression. Neurochem Res.2014;39(8):1405-1415.

[17] Golab P,Boguszewska-Czubara A,Kielbus M,et al.The rtPA increases MMP-9 activity in serum during ischaemic stroke. Neurol Neurochir Pol.2014;48(5):309-314.

[18] Maradni A,Khoshnevisan A,Mousavi SH,et al. Role of matrix metalloproteinases (MMPs) and MMP inhibitors on intracranial aneurysms: a review article. Med J Islam Repub Iran.2013;27(4):249-254.

[19] Lukaszewicz-Zajac M, Mroczko B, Slowik A. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in amyotrophic lateral sclerosis (ALS). J Neural Transm. 2014; 121(11):1387-1397.

[20] Chao HM,Chuang MJ,Liu JH,et al.Baicalein protects against retinal ischemia by antioxidation, antiapoptosis, downregulation of HIF-1alpha, VEGF, and MMP-9 and upregulation of HO-1.J Ocul Pharmacol Ther. 2013;29(6): 539-549.

[21] Lukaszewicz-Zajac M,Mroczko B,Kornhuber J,et al.Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the tumors of central nervous system (CNS). J Neural Transm.2014;121(5):469-477.

[22] Rosell A,Ortega-Aznar A,varez-Sabin J,et al.Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke.Stroke.2006; 37(6):1399-1406.

[23] Liang J,Qi Z,Liu W,et al.Normobaric hyperoxia slows blood-brain barrier damage and expands the therapeutic time window for tissue-type plasminogen activator treatment in cerebral ischemia. Stroke.2015;46(5):1344-1351.

[24] Zhao H,Wang R,Wu X,et al.Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion.J Neuroimmune Pharmacol.2015;10(1):153-161.

[25] Inzitari D, Giusti B, Nencini P,et al. MMP9 variation after thrombolysis is associated with hemorrhagic transformation of lesion and death.Stroke.2013;44(10):2901-2903.

[26] Jin X,Liu J,Yang Y,et al.Spatiotemporal evolution of blood brain barrier damage and tissue infarction within the first 3h after ischemia onset.Neurobiol Dis.2012; 48(3):309-316.

[27] Liu J,Jin X,Liu KJ,et al.Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage.J Neurosci.2012;32(9):3044-3057.

[28] Yang Y,Estrada EY,Thompson JF,et al.Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat.J Cereb Blood Flow Metab.2007; 27(4):697-709.

[29] Latour LL,Kang DW,Ezzeddine MA,et al. Early blood-brain barrier disruption in human focal brain ischemia Ann Neurol. 2004;56(4):468-477.

[30] Yang Y, Thompson JF, Taheri S,et al.Early inhibition of MMP activity in ischemic rat brain promotes expression of tight junction proteins and angiogenesis during recovery. J Cereb Blood Flow Metab 2013;33(7):1104-1114.

[31] Asahi M,Asahi K,Jung JC,et al. Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J Cereb Blood Flow Metab.2000;20(12):1681-1689.

[32] Wang X,Tsuji K, Lee SR,et al. Mechanisms of hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke. Stroke.2004; 35(11 Suppl 1): 2726-2730.