Secondary demyelination after stroke: Glial cell crosstalk

Neuroglial cells serve as the myelinating cells in the central nervous system and are essential for axonal integrity and function. Following a stroke, progressive loss of myelin occurs in white matter regions distal to the infarct core, contributing to cognitive decline and even dementia. Recent research has revealed that the central mechanism involves a cascading response triggered by disruption of the astrocyte-microglia-oligodendrocyte axis. Astrocyte-secreted lipocalin-2 acts as a key driver of myelin degradation and axonal energy crisis by inducing iron influx, triggering oxidative stress, and causing mitochondrial dysfunction. An imbalance in microglial subpopulations, along with oligodendrocyte apoptosis, further exacerbates demyelination. Although no therapies are currently approved, novel strategies targeting lipocalin-2 blockade, mitochondrial repair, and immune modulation offer new hope for preserving white matter function.