Baicalin facilitates remyelination and suppresses neuroinflammation in rats with chronic cerebral hypoperfusion by activating Wnt/β-catenin and inhibiting NF-κB signaling.

One main factor contributing to the cognitive loss in vascular dementia (VD) is white matter lesions (WMLs) carried on by chronic cerebral hypoperfusion (CCH). A secondary neuroinflammatory response to CCH accelerates the loss and limits the regeneration of oligodendrocytes, leading to progressive demyelination and insufficient remyelination in the white matter. Thus, promoting remyelination and inhibiting neuroinflammation may be an ideal therapeutic strategy. Baicalin (BAI) is known to exhibit protective effects against various inflammatory and demyelinating diseases. However, whether BAI has neuroprotective effects against CCH has not been investigated. To determine whether BAI inhibits CCH-induced demyelination and neuroinflammation, we established a model of CCH in rats by occluding the two common carotid arteries bilaterally. Our results revealed that BAI could remarkably ameliorate cognitive impairment and mitigate CA1 pyramidal neuron damage and myelin loss. BAI exhibited enhancement of remyelination by increasing the expression of myelin basic protein (MBP) and oligodendrocyte transcription factor 2 (Olig2), inhibiting the loss of oligodendrocytes and promoting oligodendrocyte regeneration in the corpus callosum of CCH rats. Furthermore, BAI modified microglia polarization to the anti-inflammatory phenotype and inhibited the release of pro-inflammatory cytokines. Mechanistically, BAI treatment significantly induced phosphorylation of glycogen synthase kinase 3β (GSK3β), enhanced the expression of β-catenin and its nuclear translocation. Simultaneously, BAI reduced the expression of nuclear NF-κB. Collectively, our results suggest that BAI ameliorates cognitive impairment in CCH-induced VD rats through its pro-remyelination and anti-inflammatory capacities, possibly by activating the Wnt/β-catenin and suppressing the NF-κB signaling.