Abstract WMP117: Exploring the Contribution of Matrix Metalloproteinase 7 in Post-stroke Gut Permeability

Background: Stroke is associated with profound immunodepression and aberrations of autonomic signaling which render the body more susceptible to infection from without and from within. Dramatic alterations of sensitive signaling networks within the gut after stroke along with systemic inflammation may promote pathways that evoke a leaky gut. The enzyme matrix metalloproteinase 7 (MMP-7) has been shown to play a prominent role in evoking gut permeability in models of systemic inflammation. We found that stoke elicits a profound increase in MMP-7 across the small intestine rapidly after injury. Hypothesis: We hypothesize that this increase in MMP-7 in the gut after stroke contributes to post-stroke gut permeability and that mice deficient in MMP-7 are protected from this effect. Methods: Young (2-5-month-old) Mmp7 knockout ( Mmp7 -/- ) and wild type (WT) control littermates were subjected to 45min-tMCAO. At 3h post-tMCAO, mice were injected intraocularly with 200mg/kg FITC-inulin at 3h post-tMCAO and euthanized 1h later. Aged (24-month-old) Mmp7 -/- mice and WT control littermates were subjected to pMCAO, injected intraocularly with 200mg/kg FITC-inulin at 47h, and euthanized 1h later. Intestinal tissue was collected, homogenized, and used to detect FITC-inulin as well as for Western blotting and RT-qPCR. Results: We demonstrate that MMP-7 levels rapidly increase throughout the small intestine after stroke at 6h and 24h post-stroke. This increase in MMP-7 is accompanied by a concurrent decrease in tight junction proteins and increase in intestinal permeability at 3h post-transient middle cerebral artery occlusion (tMCAO) and 48h post-permanent (p)MCAO. Interestingly, MMP-7 deficient mice are protected from gut permeability after stroke. Conclusion: Our data identify a novel causative agent in the phenomenon of gut permeability observed after stroke and prompt further study of the role of MMP’s in promoting gut permeability after stroke.