Details

Autor(en) / Beteiligte

• Lu, Aigang
• Suofu, Yalikun
• Guan, Fanglin
• Broderick, Joseph P.
• Wagner, Kenneth R.
• Clark, Joseph F.

Titel

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

Ist Teil von

• Neuroscience, 2013-09, Vol.253

Erscheinungsjahr

2013

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Although elevated 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 injury and development of hemorrhage transformation (HT). Here, we assessed the role of the MMP-2 KO in blood-brain-barrier 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 hour after the onset of MCAO. All mice were sacrificed 24 hours 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. 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 knockout 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.