Matrix metalloproteinase-9 and myeloperoxidase expression: quantitative analysis by antigen immunohistochemistry in a model of transient focal cerebral ischemia.
Level 5 - mechanism / opinion, no new human data
Preclinical animal research
PubMed 15060315 · doi:10.1161/01.STR.0000125861.55804.f2
What was done
Transgenic mice with 50% manganese superoxide dismutase activity (SOD2-KOs) and wild-type (WT) littermates underwent transient focal cerebral ischemia. Blood-brain barrier (BBB) breakdown was measured with Evans blue extravasation. The spatial-temporal relation between matrix metalloproteinase-9 (MMP-9) and neutrophil infiltration was assessed using quantitative immunohistochemistry for MMP-9 and myeloperoxidase at 24 and 72 hours, alongside Western blot analysis for MMP-9 protein at 6, 12, 24, 48, and 72 hours.
What was found
MMP-9 expression aligned spatially with Evans blue extravasation. In SOD2-KO mice at 72 hours, MMP-9-positive cell and vessel counts were significantly different compared with SOD2-KOs at 24 hours (P=0.004), WT mice at 24 hours (P=0.01), and WT mice at 72 hours (P=0.007). MMP-9-positive neutrophil counts remained low without significant variation by time or genotype. MMP-9 expression followed a biphasic pattern in SOD2-KOs (peaks at 6 to 12 hours and 48 to 72 hours) and was significantly elevated compared to WT controls at all time points tested (P <= 0.05).
Why it matters
The findings indicate that post-stroke BBB disruption mediated by MMP-9 is exacerbated by reduced antioxidant defense, but infiltrating neutrophils are not the primary source of MMP-9 protein in this model.
Limits
The study was conducted in a mouse model of transient focal ischemia, which may not fully capture the complexity of human ischemic stroke. Sample sizes per group and sex of the animals were not reported in the abstract. Clinical and long-term functional recovery endpoints were not assessed.
Cited by
- partial Following an ischemic stroke, there is a biphasic breakdown of the blood-brain barrier at 2 hours and 3 days that correlates with two peaks of MMP-9 expression.