Effect of intransal C3a treatment on gene expression in mouse brain cortex in the post-acute phase of ischemic stroke.

The goal of this study was to gain insight into possible mechanisms of improved neural plasticity and functional recovery folowing ischemic stroke in mice confered by a delayed intranasal treatment with complement peptide C3a (reported previously in Stokowska et al., Brian, 2017). Differential expression analysis revealed that daily intranasal treatment between day 7 and 14 post-stroke is associated with downregualtion of genes involved in inflammatory responses and glial cells reactivity, primarily astrocytes. Further, cellular deconvolution analysis pointed to C3a-dependent reduction of fraction of astrocytes with gene expression profile charcterisitc for potentially neurotoxic disease-associated astrocytes (DAAs, orignially descreibed in Alzheimer disease) and increse in fraction of homeostatic astrocytes, with expression profile indicating supportive role for neuronal function and plasticity. We conclude that the C3a-C3aR signalling modulates post-stroke reactive astrogliosis in the manner favouring neural plasticity the peri-lesional cortex. Time-course analysis of gene expression in cerebral cortex after ischemic stroke (photothrombosis). Samples were collected from ipsilesional (i.e., peri-infarct) and corresponding contralesional cortex or homotopic regions in naive (no storke) mice - encomapssing primary motor and somatosensory upper limb area. Samples were taken at baseline (naive), 7 days after stroke, i.e. before treatment initiation as well as at 14 days post-stroke, i.e. after one weak-long daily intransal treatment with C3a or PBS (vehicle); 4 mice per time-point or treatment group.