Fig. 1

Chronic hyperperfusion induces demyelination, gliosis, axonal deterioration, and cognitive impairment. a Mice were subjected to bilateral carotid artery stenosis (BCAS) by wrapping gold-plated microcoils (internal diameter, 170 μm) around the common carotid arteries. Scale bar, 3 mm. b Laser speckle contrast imaging of anaesthetised mice revealed long-lasting cerebral hypoperfusion after BCAS compared to sham-treated mice (p < 0.05, Mann–Whitney test). c Representative examples of laser speckle contrast measurements of cerebral blood flow through chronic cranial windows in mice subjected to BCAS or sham surgery before (Pre) and 7 d after the intervention. The look-up table represents arbitrary perfusion units, indicating reduced blood flow after BCAS. d Luxol Fast Blue staining of the corpus callosum (0 = no demyelination; 1 = visible fiber disarrangement; 2 = vacuoles and focal demyelination; 3 = widespread/continuous demyelination) revealed demyelination 7 d and 42 d after BCAS (n = 6 for each group; p < 0.05, Kruskal-Wallis test followed by Dunn’s multiple comparisons test). e-g The area covered by GFAP-positive astrocytes, astrocyte diameter and astrocyte process length were increased in mice subjected to BCAS in the corpus callosum, indicating reactive astrogliosis (n = 6 for each group; p < 0.05, Mann–Whitney test). h Mild reactive microgliosis was also evident 6 weeks after BCAS, indicated by an increase in Iba1-positive cells (n = 6 for each group; p < 0.05, Mann–Whitney test). i In parallel, there was a decrease in the density of SMI312-positive axons in the corpus callosum after 6 weeks, indicating axonal loss (n = 6 for each group; p < 0.05, Mann–Whitney test). j Electrochemiluminescence measurements revealed an increase in the pro-inflammatory cytokines IL-1 and IL-6 in homogenates from the corpus callosum (n = 8 for each group; p < 0.05, Mann–Whitney test)