Differential roles of neuro-inflammatory regulator, MAPK11 in cortex and hippocampus following post-stroke cognitive impairments in rats
Ischaemic stroke is the leading cause of long-term cognitive impairments, affecting brain regions vulnerable to memory and learning, with complex and diverse mechanisms. The hippocampus along with cortex is crucial for shaping essential cognitive functions in post-stroke cognitive impairments. However, the region-specific neural, molecular and cellular mechanistic response to ischaemic-damage, particularly the role of inflammation is rarely explored. In this context, we carried out post-stroke region-specific research, including the development of BCCAo model and the neurobehavioral assessment targeting memory and learning deficits. Here, we performed NGS and depth-in-network analysis of the isolated cortical and hippocampal regions of the post-stroke BCCAo model, revealing 13 significant neurodegenerative hub genes including Map2k6 and Mapk11, which play crucial roles in inflammation-mediated post-stroke neurodegenerative cascades. Significant upregulation of MAP2K6/MAPK11 in the cortex of ischaemia-treated rats was observed, whereas its comparatively diminished expression in the hippocampus demand exploration of region-specific study in chronic ischaemic conditions. Furthermore, we demonstrated the role of MAPK11 as neuroinflammatory regulator and alleviating the cognitive impairments by including the upstream Akt/GSK3 beta pathway components. Our findings not only highlighted the potential roles of MAP2K6/MAPK11 driving neuroinflammatory processes regulating ischaemic cascades but also pinpointed the hippocampus relative resilience preserving cognitive function. Targeting MAPK11 and its associated neuroinflammatory pathways in the cortex to mitigate PSCI holds promise as a therapeutic strategy in chronic ischaemia.