Plasticity of perisynaptic astroglia during ischemia-induced spreading depolarization.

High astroglial capacity for glutamate and potassium clearance aids in recovering spreading depolarization (SD)-evoked disturbance of ion homeostasis during stroke. Since perisynaptic astroglia cannot be imaged with diffraction-limited light microscopy, nothing is known about the impact of SD on the ultrastructure of a tripartite synapse. We used serial section electron microscopy to assess astroglial synaptic coverage in the sensorimotor cortex of urethane-anesthetized male and female mice during and after SD evoked by transient bilateral common carotid artery occlusion. At the subcellular level, astroglial mitochondria were remarkably resilient to SD compared to dendritic mitochondria that were fragmented by SD. Overall, 482 synapses in Sham' during SD' and `Recovery' groups were randomly selected and analyzed in 3D. Perisynaptic astroglia was present at the axon-spine interface (ASI) during SD and after recovery. Astrocytic processes were more likely found at large synapses on mushroom spines after recovery, while the length of the ASI perimeter surrounded by astroglia has also significantly increased at large synapses. These findings suggest that as larger synapses have a bigger capacity for neurotransmitter release during SD, they attract astroglial processes to their perimeter during recovery, limiting extrasynaptic glutamate escape and further enhancing the astrocytic ability to protect synapses in stroke.