Journal
NEUROSCIENCE LETTERS
Volume 512, Issue 2, Pages 67-71Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2012.01.007
Keywords
NAD(+); Brain ischemia; Autophagy; Infarct formation; Neurological deficits
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Funding
- Pujiang Scholar Program Award [09PJ1405900]
- National Key Basic Research '973 Program Grant' [2010CB834306]
- Chinese National Science Foundation [81171098]
- Key Shanghai Jiao Tong University
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Nicotinamide adenine dinuleotide (NAD(+)) plays critical roles in multiple biological functions. Previous studies have indicated that NAD(+) treatment decreases oxidative stress-induced death of primary neurons and astrocytes. Intranasal administration of NAD(+) also reduces brain damage in a rat model of transient focal brain ischemia. However, the mechanisms underlying this protective effect remain unknown. In this study, we used a mouse model of brain ischemia to test our hypothesis that NAD(+) decreases ischemic brain damage partially by preventing autophagy. Adult male mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 90 min, and NAD(+) was administered intraperitoneally (i.p.) immediately after reperfusion started. We found that administration with 50 mg/kg NAD(+) led to significant decreases in infarct size, edema formation, and neurological deficits at 48 h after ischemia. NAD(+) administration also significantly decreased brain ischemia-induced autophagy in the cortex and hippocampus. We further found that prevention of autophagy by 3-methyladenine (3-MA), a selective autophagy inhibitor, significantly reduced ischemic brain damage, suggesting an important role of autophagy in the ischemic brain injury in our animal model. Collectively, our findings have suggested that NMD+ administration decreases ischemic brain damage at least partially by blocking autophagy. This is the first suggested mechanism regarding the protective effects of NAD(+) in cerebral ischemia, which further highlights the promise of NAD(+) for treating brain ischemia. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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