Transient global cerebral ischemia induces rapid and sustained reorganization of synaptic structures

Abstract

Ischemia can cause rapid neuronal damage. Previous studies have suggested that synaptic structures and cortical functions can be rescued if therapeutic interventions are applied in time, but the structural basis for this resilience remains incompletely understood. Here, we investigated the restoration of synaptic structures and postischemic plasticity of dendritic spines in the somatosensory cortices of mice by taking advantage of a reversible global cerebral ischemia model. Intravital two-photon imaging revealed that although dendritic structures were rapidly distorted after global ischemia, only a small percentage of spines were actually lost after transient ischemia. Electron microscopy indicated that most presynaptic electron-dense structures were still apposed to postsynaptic densities, and that the majority of disrupted synaptic structures were rapidly reinstated following reperfusion after transient ischemia. Repeated imaging suggested that restored dendrites survived the initial ischemia –reperfusion challenge. Importantly, spines on the restored dendrites underwent a rapid and sustained structural reorganization following transient ischemia. These findings suggested that disrupted synapses during transient ischemia could be rapidly restored after ischemia/reperfusion, and that restored dendritic structures remained plastic to rebuild the cortical network.