Sustained ICP Elevation Is a Driver of Spatial Memory Deficits After Intraventricular Hemorrhage and Leads to Activation of Distinct Microglial Signaling Pathways

In this study, we show that intraventricular hemorrhage only leads to a significant spatial memory deficit in the Morris water maze if it occurs in the setting of an elevated intracranial pressure (ICP). Histopathological analysis of these IVH  + ICP animals did not show evidence of neuronal degeneration in the hippocampal formation after 2 weeks but instead showed significant microglial activation measured by lacunarity and fractal dimensions. RNA sequencing of the hippocampus showed distinct enrichment of genes in the IVH + ICP group but not in IVH alone having activated microglial signaling pathways. The most significantly activated signaling pathway was the classical complement pathway, which is used by microglia to remove synapses, followed by activation of the Fc receptor and DAP12 pathways. Thus, our study lays the g roundwork for identifying signaling pathways that could be targeted to ameliorate behavioral deficits after IVH.
Source: Translational Stroke Research - Category: Neurology Source Type: research