Journal
NEUROSCIENCE
Volume 253, Issue -, Pages 361-367Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2013.08.068
Keywords
cerebral ischemia; hemorrhagic transformation; MMP-2 knockout; mice
Categories
Funding
- NIH [NS44283, NS50569, NS57367]
Ask authors/readers for more resources
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 1 h of ischemia and 23 h of reperfusion. Middle cerebral artery occlusion (MCAO) was performed in MMP-2 KO mice. Reperfusion was started 1 h after the onset of MCAO. All mice were sacrificed 24 h 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. Published by Elsevier Ltd. on behalf of IBRO.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available