Despite the crucial role of perineuronal nets (PNNs) in neural plasticity and neurological disorders, their ultrastructural organization remains largely unresolved. We have developed a novel approach combining superresolution structured illumination microscopy (SR-SIM) and mathematical reconstruction that allows for quantitative analysis of PNN topology. Since perineuronal matrix is capable to restrict neural plasticity but at the same time is necessary to maintain synapses, we hypothesized that a beneficial post stroke recovery requires a reversible loosening of PNNs. Our results indicated that focal cerebral ischemia induces partial depletion of PNNs and that mild hypoperfusion not associated with ischemic injury can induce ultra-structural rearrangements in visually intact meshworks. In line with the activation of neural plasticity under mild stress stimuli, we provide evidence that topological conversion of PNNs can support post stroke neural rewiring.
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