Complexity of Damage-Associated Molecular Pattern Molecule Expression Profile in Porcine Brain Affected by Ischemic Stroke

TL;DR

This study explores how molecules linked to brain injury change over time in pigs after a stroke, revealing patterns of inflammation and healing.

Contribution

The study reveals time-dependent changes in DAMP expression in a porcine model of ischemic stroke, linking inflammation and vascular remodeling.

Findings

Increased expression of calcium-binding proteins, peroxiredoxins, heat shock proteins, and interleukins within 24 hours post-stroke.

Multiple DAMPs and vascular endothelial growth factor A (VEGFA) were up-regulated by day 7 post-stroke.

Systemic inflammatory response was observed through altered serum levels of interleukins.

Abstract

Studies using large animal models are essential for better understanding the molecular processes underlying neurological diseases, including ischemic stroke, and serve as a robust foundation for evaluating potential therapies. To better understand the complex role of damage-associated molecular pattern molecules (DAMPs) after ischemia, we aimed to determine their expression in the porcine brain affected by ischemic stroke at four time points: 6 h, 24 h, 3 days and 7 days post-stroke. Within the first 24 h after the stroke, we observed the increased expression of several key factors, including calcium-binding proteins, peroxiredoxins, heat shock proteins and interleukins (1α and 1β, IL10, IL17α). Moreover, by day 7, multiple DAMPs were up-regulated, coinciding with an enhanced expression of vascular endothelial growth factor A (VEGFA) in the affected hemisphere. The effects of ischemic stroke were also evident systemically, as indicated by the altered serum levels of both pro- and anti-inflammatory interleukins, reflecting dynamic inflammatory response. To conclude, our findings provide new insights about the time-dependent DAMP activity in a large animal model of ischemic stroke, highlighting the simultaneous occurrence of an ongoing inflammatory response and the possible initiation of vascular remodeling as early as one week after stroke onset.

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