| Objective:To establish the mouse model of chronic cerebral hypoperfusion white matter damage characterizing features of vascular cognitive impairmentMethods:SPF male C57BL/6J, weighted24-29g, were subjected to bilateral common carotid artery stenosis(BCAS) to induce chronic cerebral hypoperfusion. The inner diameter of selected microcoils was0.18mm. The blood flow of cerebral blood flow(CBF) was measured2hours after BCAS with laser Doppler flowmeter;7T Magnetic Resonance Imaging was used to observe and calculate the white matter lesion; The cognition function was estimated by eight-arm maze task on day30after BCAS; In the end, Luxol Fast Blue staining and immunofluorescence staining were performed to assess and analyze white matter demyelination、nerve fiber integrity、the neuron survival、activation of astrocyte and microgliaResults:(1) It is successful to establish the BCAS mouse model. At2hours, the CBF values (ratio to the preoperative value) decreased to60-70%significantly comnpared with control;(2) LFB staining demonstrated a significant demyelination changes in white matter regions,such as CC、IC、CPu;(3) There was a significant change in DTI correlated parameter FA and RD, indicating glia-axonal integrity management and demyelination changes of white matter regions in BCAS groups. However, no change in AD value indicating axonal damage was observed;(4) In the working memory tasks test with the8-arm radial maze, the BCAS mice made significantly more errors than the control mice (P <0.001). Again, there were no detectable differences in the reference memory tasks between the groups. There existed significant correlation between white matter lesion demonstrated by DTI and working memory errors, P<0.05;(5) At day30after BCAS, immunofluorescence and MR spectroscopy demonstrated no gray matter structural and functional changes in hippocampus and cortex, indicating no gray matter damage occurred;(6) The proliferation of activated microglia and astroglia was observed in the white matter after BCAS.Conclusions:At day30after BCAS, working memory deficits as well as white matter changes、glia proliferation were apparent in the mice. Since working memory deficit is attributable to damage of the frontal-subcortical circuits, our data suggest that the BCAS model is useful to evaluate the substrates of subcortical vascular dementia. No gray matter damage was found in BCAS groups. Objective:To investigate white matter lesion in different hypo-perfusion process of the BCAS mouse model.Methods:Adult C57B1/6male mice were subjected to BCAS mouse model using external microcoils with inner diameter0.18mm, then7T Magnetic Resonance Imaging was used to observe and calculate the white matter lesion at3day,7day,1month, and3month after BCAS; The brains were then removed and examined with immunofluorescence for markers of axon-glial integrity (assessed by MAG) and integrity of axons (assessed by NF-20).Results:(1) On day3or day10after BCAS, significant reduction in fractional anisotropy (FA) was observed in the optic tract、internal capsule、the median part of corpus callosum. In the process of hypoperfusion, there was no significant changes of FA value; Immunofluorescence(IF) staining of MAG also demonstrated decreased MAG expression in the median part of corpus callosum; Both FA and MAG correlate with markers of myelin integrity/degradation.(2) After3months’ BCAS, significant reduction in axial diffusivity (AD) was observed in the optic tract、internal capsule while there was no obvious change in other white matter regions; the IF staining of NF exhibited no changes of IF density in white matter region among groups.Conclusions:The damage of white matter integrity occurred on day3or day10after BCAS, mainly in optic tract、internal capsule、the median part of corpus callosum; With the progress of hypoperfusion, optic tract and internal capsule exhibited axonal damage or degenerative changes as demonstrated by decreased AD value. |
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