Abstract
Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia,how-ever no effective treatments are available.Here,based on magnetic resonance imaging studies of patients with white matter damage,we found that this damage is associated with disorganized cortical structure.In a mouse model,optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligo-dendrocyte progenitor cell(OPC)proliferation,remyelination in the corpus callosum,and recovery of cognitive ability after cerebral hypoperfusion.The therapeutic effect of such stimulation was restricted to the upper layers of the cortex,but also spanned a wide time window after ischemia.Mechanistically,enhancement of glutamater-gic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons.Additionally,skin stroking,an easier method to translate into clinical practice,activated the somatosensory cortex,thereby promoting OPC proliferation,remyelination and cognitive recovery following cerebral hypoperfusion.In summary,we demonstrated that activating glutamatergic neurons in the somatosen-sory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion.It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.
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