Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice

Neurobiology of Disease

Sarah Jane George¹  Andrew Baker²  Lorraine E. Kerr³  James McCulloch⁴  W. Colin Duncan⁵  Sandra Magnoni⁶  Karen Horsburgh⁷ 

[1] Corresponding author. Dipartimento di Anestesia e Rianimazione, Terapia Intensiva Neuroscienze, Ospedale Maggiore Policlinico, Via Sforza 35, 20122, Milan, Italy. Fax: [phone].;Department of Anesthesia and Intensive Care, Ospedale Maggiore Policlinico, IRCCS, Via Sforza 35, 20122, Milan, Italy;Bristol Heart Institute, University of Bristol Level 7, Bristol BS2 8HW, UK;Department of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK;Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK;Division of Neuroscience, University of Edinburgh, Edinburgh EH8 9JZ, UK;Fujisawa Institute of Neuroscience (FINE), University of Edinburgh, Edinburgh EH8 9JZ, UK;

关键词: Matrix metalloproteinases (MMPs);    Cerebral ischemia;    Mice;    Proteolytic activity;   

DOI  :  

来源: DOAJ

【 摘 要 】

Abnormal expression and activity of matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral disease such as ischemic injury. In this study, we compared the cellular localization, expression, and activity of MMP-2 and -9 in relation to the evolution of neuronal damage 24 and 72 h after transient global ischemia. In response to ischemia, there was a generalized increase in cellular MMP-2 immunoreactivity at 24-h reperfusion (in neurons, glia and vessels) whereas at 72-h reperfusion the increase in MMP-2 was predominantly in glia. These glial alterations contributed to a significant increase in pro MMP-2 levels in ischemic regions (P < 0.01) as measured by zymography. In contrast, MMP-9 was predominantly upregulated in neurons and this was significantly different to shams at 24- and 72-h reperfusion after ischemia (P < 0.05). Notably, a dramatic increase in proteolytic activity in neurons was observed 24 h after ischemia and this response was absent at 72 h post-ischemia. The present data are supportive of a role for MMPs in contributing to neuronal injury after ischemia.

【 授权许可】

Unknown