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

• Published in: International journal of molecular sciences Vol. 26; no. 8; p. 3702
• Main Authors: Golubczyk, Dominika, Mowinska, Aleksandra, Holak, Piotr, Walczak, Piotr, Janowski, Miroslaw, Malysz-Cymborska, Izabela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.04.2025; MDPI
• Subjects: Alarmins - genetics; Alarmins - metabolism; Analysis; Animals; Binding proteins; Brain - metabolism; Brain - pathology; Brain Ischemia - metabolism; Brain research; Cytokines; Disease Models, Animal; Endothelial growth factors; Gene expression; Heat shock proteins; Interleukins; Ischemia; Ischemic Stroke - genetics; Ischemic Stroke - metabolism; Ischemic Stroke - pathology; Molecules; Nervous system diseases; Protein binding; Proteins; Stroke (Disease); Swine; Tissues; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Poland; California; United States; Germany; animal model; brain; stroke; DAMPs; pig
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms26083702

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.