Preventive Effects of Rapamycin on Inflammation and Capillary Degeneration in a Rat Model of NMDA-Induced Retinal Injury

被引:14
作者
Aoki, Yuto [1 ]
Nakahara, Tsutomu [1 ]
Asano, Daiki [1 ]
Ushikubo, Hiroko [1 ]
Mori, Asami [1 ]
Sakamoto, Kenji [1 ]
Ishii, Kunio [1 ]
机构
[1] Kitasato Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol, Minato Ku, Tokyo 1088641, Japan
关键词
endothelial cell; excitotoxicity; leukocyte; mammalian target of rapamycin; microglia; REPERFUSION INJURY; AXON REGENERATION; ISCHEMIA; AUTOPHAGY; MICROGLIA/MACROPHAGES; NEUROPROTECTION; SIMILARITIES; MECHANISM; PATHWAY; MK-801;
D O I
10.1248/bpb.b14-00631
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Inhibitors of the mammalian target of rapamycin (mTOR) have been shown to protect against neuronal injury, but the mechanisms underlying this effect are not fully understood. The present study aimed to examine the effects of rapamycin, an inhibitor of the mTOR pathway, on inflammation and capillary degeneration in a rat model of N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity. Inflammation and capillary degeneration were evaluated by counting the numbers of CD45-positive leukocytes and Iba1-positive microglia, and by measuring the length of empty basement membrane sleeves, respectively. Marked increases in the numbers of leukocytes and microglia were observed 1 d after intravitreal injection of NMDA (200 nmol), and significant capillary degeneration was observed after 7d. These NMDA-induced changes were significantly reduced by the simultaneous injection of rapamycin (20 nmol) with NMDA. These results suggest that rapamycin has preventive effects on inflammation and capillary degeneration during retinal injury.
引用
收藏
页码:321 / 324
页数:4
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