OBJECTIVE The aim of this study was to investigate the protection of minocycline in chronic ischemic cerebral white matter injury.METHODS Adult male mice(C57BL/6 strain) were subjected to right unilateral common carotid arteries occlusion(rUCCAO),and treated with minocycline(25 mg·kg-1) once a day for the following ways: D 0-35,D 0-3,D 0-7,D 4-7,D 4-14,D 4-35,D 15-35,or D 0-3 and D 15-35.Object recognition test,and Morris water maze test were performed at 27 d and immunohistochemical analyses were performed at 35 d after rUCCAO.RESULTS We found that administration of minocycline D 0-35,D 0-3,D 15-35,or D 0-3 and D 15-35 significantly ameliorated the decrease of myelin basic protein(MBP) expression and cognitive impairment evaluated by object recognition test,and Morris water maze test after rUCCAO.However,administration of minocycline D 0-7,or D 4-35 did not induce obvious effect and administration of minocycline D 4-7,or D 4-14 decreased the myelin proteolipid protein(PLP) expression and aggravated cognitive impairment.CC1+ mature oligodendroglia decreased after rUCCAO,while NG2+ oligodendrocyte progenitor cell(OPC) and Olig2+ total oligodendroglia increased at 3 d and continued until 7 d,but decreased from 14 d after rUCCAO.Administration of minocycline D 0-3 inhibited the reduction of mature oligodendroglia and promoted the proliferation of OPC.Administration of minocycline D 4-14 showed no effect on mature but reduced the number of OPC and total oligodendroglia.Administration of minocycline D 15-28 reversed the reduction of mature oligodendroglia and OPC.CONCLUSION These data suggest that minocycline has multiple effects on white matter injury after rUCCAO in mice.At the early stage and the later stage minocycline shows the protection on rUCCAO,while at the middle stage minocycline has a damage effect on rUCCAO. OBJECTIVE The aim of this study was to investigate the protection of minocycline in chronic ischemic cerebral white matter injury. METHODS Adult male mice (C57BL / 6 strain) were subjected to right unilateral common carotid arteries occlusion (rUCCAO), and treated with minocycline (25 mg · kg -1) once a day for the following ways: D 0-35, D 0-3, D 0-7, D 4-7, D 4-14, D 4-35, D 15-35, or D 0-3 and D 15-35. Object recognition test, and Morris water maze test were performed at 27 d and immunohistochemical analyzes were performed at 35 d after rUCCAO.RESULTS We found that administration of minocycline D 0-35, D 0- 3, D 15-35, or D 0-3 and D 15-35 significantly ameliorated the decrease of myelin basic protein (MBP) expression and cognitive impairment evaluated by object recognition test, and Morris water maze test after rUCCAO. However, administration of minocycline D 0-7, or D 4-35 did not induce obvious effect and administration of minocycline D 4-7, or D 4-14 decreased the myelin proteolipid protein (PLP) expression and aggravated cognitive impairment. CC1 + mature oligodendroglia decreased after rUCCAO, while NG2 + oligodendrocyte progenitor cell (OPC) and Olig2 + total oligodendroglia increased at 3 d and continued until 7 d, but decreased from 14 d after rUCCAO.Administration of minocycline D 0-3 inhibited the reduction of mature oligodendroglia and promoted the proliferation of OPC. Administration of minocycline D 4-14 showed no effect on mature but reduced the number of OPC and total oligodendroglia. Administration of minocycline D 15-2 reversed the reduction of mature oligodendroglia and OPC. CONCLUSION These data suggest that minocycline has multiple effects on white matter injury after rUCCAO in mice. At the early stage and the later stage minocycline shows the protection on rUCCAO, while at the middle stage minocycline has a damage effect on rUCCAO.