期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 35, 期 3, 页码 382-391出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2014.210
关键词
axonal outgrowth; chronic hypoperfusion; L-carnitine; oxidative steess; stroke
资金
- High Technology Research Center grant
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Foundation for Strategic Research Projects in Private Universities from MEXT [S1311011]
- Comprehensive Brain Science Network (CBSN)
- Grants-in-Aid for Scientific Research [25460276, 221S0003, 26111519] Funding Source: KAKEN
Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent With a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapannycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model.
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