GSE253476 Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation

Contributors : Andrew S Mendiola ; Katerina Akassoglou ; Jae K RyuSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTraumatic brain injury (TBI) causes significant blood-brain barrier (BBB) breakdown, resulting in the extravasation of blood proteins into the brain. The impact of blood proteins, especially fibrinogen, on inflammation and neurodegeneration post-TBI is not fully understood, highlighting a critical gap in our comprehension of TBI pathology and its connection to innate immune activation. We combined vascular casting with 3D imaging of solvent-cleared organs (uDISCO) to study the spatial distribution of the blood coagulation protein fibrinogen in large, intact brain volumes and assessed the temporal regulation of the fibrin(ogen) deposition by immunohistochemistry in a murine model of TBI. Fibrin(ogen) deposition and innate immune cell markers were co-localized by immunohistochemistry in mouse and human brains after TBI. We assessed the role of fibrinogen in TBI using unbiased transcriptomics, flow cytometry and immunohistochemistry for innate immune and neuronal markers in Fgg γ390–396A knock-in mice, which express a mutant fibrinogen that retains normal clotting function, but lacks the γ390–396 binding motif to CD11b/CD18 integrin receptor. We show that cerebral fibrinogen deposits were associated with activated innate immune cells in both human and murine TBI. Gen etic elimination of fibrin-CD11b interaction reduced pe...

Source: GEO: Gene Expression Omnibus - April 16, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research