Matrix metalloproteinase-2 deletions protect against hemorrhagic transformation after 1 h of cerebral ischemia and 23 h of reperfusion.

Abstract

Although elevated matrix metalloproteinase (MMP)-2 levels were highly related to the degradation of tight junction (TJ) proteins and basal lamina and neuronal injury after ischemia, until very recently, little experimental evidence was available to test the role of the MMP-2 knockout (KO) in blood-brain-barrier (BBB) injury and the development of hemorrhage transformation (HT). Here, we assessed the role of the MMP-2 KO in BBB injury, HT and other brain injuries after 1h of ischemia and 23 h of reperfusion. Middle cerebral artery occlusion (MCAO) was performed in MMP-2 KO mice. Reperfusion was started 1h after the onset of MCAO. All mice were sacrificed 24h after the MCAO. MMP-2 deficiency reduced the decrease in protein levels of collagen IV and cellular membrane occludin (p<0.01 and 0.05 vs. wild-type (WT), respectively) and attenuated increase in cytosol occludin level in ischemic brain (p<0.01 vs. WT). The hemorrhage volume and brain infarction were significantly decreased in both the cortex and striatum in the MMP-2 KO mice (p<0.01 vs. WT). The MMP-2 KO also had reduced brain swelling in the cortex and improved neurological deficits (p<0.01 vs. WT). These studies provide direct evidence that targeting MMP-2 will effectively protect against collagen and occludin loss and HT after ischemia and reperfusion.

• Authors: A Lu, Y Suofu, F Guan, J P Broderick, K R Wagner, J F Clark
• Journal: Neuroscience (Neuroscience) Vol. 253 Pg. 361-7 (Dec 03 2013) ISSN: 1873-7544 [Electronic] United States
• PMID: 24035828 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Occludin
• Collagen
• Matrix Metalloproteinase 2

Topics

• Analysis of Variance
• Animals
• Brain Edema (enzymology, etiology)
• Brain Infarction (enzymology, etiology)
• Brain Ischemia (complications, genetics)
• Cell Membrane (metabolism, pathology)
• Cerebral Hemorrhage (enzymology, etiology, prevention & control)
• Collagen (metabolism)
• Cytosol (metabolism, pathology)
• Disease Models, Animal
• Gene Expression Regulation (genetics)
• Matrix Metalloproteinase 2 (deficiency)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Occludin (metabolism)
• Reperfusion Injury (genetics, physiopathology)