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Objective Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia, with characteristics of white matter damage and cognitive behavior decline,yet the detailed pathogenic mechanism is still unclear.Our previous and others works imply that microglial activation and reactive astrocytes participate in the development of SIVD.IL-1β is the major proinflammatory cytokines secreted by glia, however, its role in SIVD is not appreciated.Methods IL-1 receptor knockout (IL-1R KO)mice or wide type mice (C57BL/6 strain) were subjected to right unilateral common carotid arteries occlusion (rUCCAO), a mouse model of SIVD, and treated with IL-1 receptor antagonist (IL-1Ra).Immunohistochemical,Western blot, electron microscopy, TUNEL analyses,object recognition test and Morris water maze test were performed after rUCCAO.Results We found that IL-1β,mainly derived from astrocyte, elevated from 1 d to 7 d and returned to baseline at 14d in SVZ (subventricularzone) and corpus callosum after rUCCAO.Administration of IL-1 Ra from 1 d to 7 d, rescued the downregulation of MBP caused by ischemia both on day 8 and day 28.Electron microscopy showedthat IL-1 Ra treatment increased the number of myelinated axons and myelin thickness compared with saline-treated group 28 d after rUCCAO.Moreover, IL-1 Ra administration significantlyelevated the discrimination index in object cognition test and reduced escape latencies during the acquisitiontrialsin Morris water test 28d afterrUCCAO,which presents improved learning and memory ability.While in IL-1R KO mice, there is no difference between rUCCAO group and sham group both in myelin change and cognitive impairment.We also found that IL-1 Ra reversed the decreased number of NG2+ OPCs caused by rUCCAO in corpus callosum on day 8, however IL-1R KO mice did not display obvious loss of OPCs after ischemia.The differences in OPC number appears to result from the inhibition of OPCs recruitment from SVZ to corpus callosum by IL-1β, since there is no difference in the number of oligodendrocytes undergoing proliferation both in corpus callosum and SVZ, performed by Brdu (5-bromo, 2deoxyuridine) labeling, and in apoptosis measured by cleaved caspase-3 expression and TUNEL+ olig2+ cells counting, between rUCCAO group and IL-1Ra treated group.Besides, we found that IL-1βdecreased the number of migrating cells in rostral migratory stream after rUCCAO.Conclusion IL-1β is a cause of poor remyelination in SIVD probably through blocking OPCs migration.It may serve as a potential therapeutic target for SIVD.