Abstract
OBJECTIVE: To study the neuroprotective mechanism of minocycline against vascular cognitive impairment after cerebral ischemia. METHODS: The rat model with vascular cognitive impairment was established by permanent bilateral common carotid artery occlusion (BCCAO). The observing time-points were determined at 4, 8 and 16 weeks after BCCAO. Animals were randomly divided into sham-operated group (n = 6), model group (subdivided into 3 groups: 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6), and minocycline group (subdivided into 3 groups: 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6). Minocycline was administered by douche via stomach after BCCAO until sacrifice. Glial fibrillary acidic protein (GFAP) was examined by Western blotting and immunohistochemistry. Levels of cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB) were measured by immunohistochemistry. IL-1beta and TNF-alpha levels were tested with ELISA method. RESULTS: Levels of GFAP, COX-2, NF-kappaB, IL-1beta and TNF-alpha were all up-regulated after permanent BCCAO, which could be significantly inhibited by minocycline. CONCLUSION: Minocycline could ameliorate the inflammation and oxidative stress in the hippocampus of the vascular cognitive impairment rat model.