期刊
MOLECULAR NEUROBIOLOGY
卷 53, 期 9, 页码 6482-6488出版社
SPRINGER
DOI: 10.1007/s12035-015-9554-y
关键词
Omega-3 polyunsaturated fatty acids; DHA; Ischemia; ROS
资金
- Macao Science and Technology Development Fund [018/2013/A1, MRG003/SHX/2014/ICMS]
- University of Macau [MYRG122 (Y1-L3)-ICMS12-SHX, MYRG110 (Y1-L2)- ICMS13-SHX]
- Hundred Talents program, Qing Lan Project of Nanjing Normal University
- Jiangsu Provincial Natural Science Foundation [BK20140917]
- National Natural Science Foundation of China [81501164]
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential in a variety of neurological disorders, including ischemic stroke. However, the underlying mechanisms still lack investigation. Here, we report that cultured cortical neurons isolated from fat-1 mice with high endogenous n-3 PUFAs were tolerant to oxygen-glucose deprivation/reperfusion (OGD/R) injury. Fat-1 neurons exhibited significantly attenuated reactive oxygen species (ROS) activation induced by OGD/R injury, upregulated antiapoptotic proteins Bcl-2 and Bcl-xL, and reduced cleaved caspase-3. Exogenous administration of docosahexaenoic acid (DHA), a major component of the n-3 PUFA family, resulted in similar protective effects on cultured cortex neurons. We further verified the protective effects of n-3 PUFAs in vivo, using a mini ischemic model with a reproducible cortical infarct and manifest function deficits by occlusion of the distal branch of the middle cerebral artery with focused femtosecond laser pulses. The Fat-1 animals showed decreased ROS expression and higher level of glutathione in the injured brain, associated with improved functional recovery. We therefore provide evidence that n-3 PUFAs exert their protective effects against ischemic injury both in vitro and in vivo, partly through inhibiting ROS activation.
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