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Korean J Physiol Pharmacol. 2011 Apr;15(2):115-22. doi: 10.4196/kjpp.2011.15.2.115. Epub 2011 Apr 30.

Matrix metalloproteinase inhibitors attenuate neuroinflammation following focal cerebral ischemia in mice.

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1
Department of Pharmacology, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University School of Medicine, Yangsan 626-870, Korea.

Abstract

The aim of this study was to investigate whether matrix metalloproteinase (MMP) inhibitors attenuate neuroinflammation in an ischemic brain following photothrombotic cortical ischemia in mice. Male C57BL/6 mice were anesthetized, and Rose Bengal was systemically administered. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold white light. MMP inhibitors, such as doxycycline, minocycline, and batimastat, significantly reduced the cerebral infarct size, and the expressions of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and indoleamine 2,3-dioxygenase (IDO). However, they had no effect on the expressions of heme oxygenase-1 and neuroglobin in the ischemic cortex. These results suggest that MMP inhibitors attenuate ischemic brain injury by decreasing the expression levels of MCP-1, TNF-α, and IDO, thereby providing a therapeutic benefit against cerebral ischemia.

KEYWORDS:

Indoleamine 2,3-dioxygenase; Matrix metalloproteinase inhibitor; Monocyte chemotactic protein-1; Photothrombotic cortical ischemia; Tumor necrosis factor-α

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