WHOLE-BRAIN NETWORK ANALYSIS REVEALS FUNCTIONAL AND STRUCTURAL DISCONNECTIONS IN A MOUSE MODEL FOR STROKE

Ischemic stroke represents one of the major causes of mortality and long-term disability worldwide. It arises from a disruption of cerebral blood supply, triggering neuronal and glial injury via multiple cell death pathways. The ischemic penumbra undergoes rearrangements and neuronal plasticity mechanisms, playing a crucial role in determining the extent of irreversible injury. Beyond local disruptions, stroke causes both direct and indirect disconnections in functional connectivity, inducing remote dysfunction in structurally intact brain regions connected to the lesion and altering whole-brain network communication. These network-level disconnections may contribute to increased functional impairment, thereby modulating post-stroke recovery outcomes. In this scenario, our research aims to investigate stroke-induced alterations in neuronal activity at both local and whole-brain network levels. After characterizing the stroke mouse model of permanent distal middle cerebral artery occlusion (dMCAO), we described functional neuronal activity patterns via mesoscale calcium imaging. Furthermore, to evaluate the long-range effects of the focal brain injury, the anatomical disconnections were then characterized through a tractography analysis, helping us to identify both the preserved and impaired pathways after the ischaemic event occurred. Finally, we took advantage of motor and cognitive behavioral tasks (gridwalk, water grasping and Y maze tests), to assess functional deficits induced by the stroke onset, establishing correlations between the altered neuronal activity and the recovery outcomes. This integrated approach allowed us to elucidate the relationship between focal lesions and wide-field network alterations, focusing on the emergence of aberrant activity patterns within the perilesional area and their spread throughout other brain regions.