Response to Letter Regarding Article, “Matrix Metalloprotease 3 Exacerbates Hemorrhagic Transformation and Worsens Functional Outcomes in Hyperglycemic Stroke”
Matrix metalloprotease 3 (MMP3) is a zinc endopeptidase that has the ability to digest and degrade the basal lamina and tight junction proteins causing increased blood–brain barrier disruption.1 We showed that acute hyperglycemia increased MMP3 activity in the brain after stroke and this was associated with exacerbated cerebral hemorrhage and worse functional outcomes. Both pharmacological and molecular inhibition of MMP3 reduced the injury and improved the outcomes.
It was previously shown that MMP3 plays a role in degrading tight junction proteins like occludin and claudin-5 in several neurological disorders.2,3 However, this was not studied specifically in acute hyperglycemic stroke and we agree that this would be a good point for future studies.
We were also interested in showing the expression of MMP3 in the neurovascular unit, especially the vasculature, to correlate it to the bleeding occurring after stroke. It was previously shown that MMP3 released in response to neurodegeneration causes microglial activation and release of inflammatory cytokines like tumor necrosis factor-α and interleukin-1B. In addition, activated microglia showed to express and release more MMP3 in response to neuroinflammation. This was extensively studied and reviewed by Kim and Hwang.4 Accordingly, we think that microglial activation may be playing a crucial role in MMP3 induction and activation in hyperglycemic stroke and again, this may be another good point for future studies.
Sherif Hafez, PhD
Adviye Ergul, MD, PhD
Charlie Norwood VA Medical Center
Medical College of Georgia
Sources of Funding
Dr Ergul is a Research Career Scientist at the Charlie Norwood Veterans Affairs Medical Center in Augusta, Georgia. This study was supported in part by Veterans Affairs (VA) Merit Award (BX000347), VA Research Career Scientists Award, and National Institutes of Health (R01NS083559) to Adviye Ergul and American Heart Association Predoctoral Fellowship (13PRE17090026) to Sherif Hafez. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.
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