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NAMPT inhibitor protects ischemic neuronal injury in rat brain via anti-neuroinflammation.

Authors: Chen, Chen-Xiang  Huang, Jing  Tu, Ga-Qi  Lu, Jia-Tong  Xie, Xian  Zhao, Bing  Wu, Ming  Shi, Qiao-Juan  Fang, San-Hua  Wei, Er-Qing  Zhang, Wei-Ping  Lu, Yun-Bi 
Citation: Chen CX, etal., Neuroscience. 2017 Jul 25;356:193-206. doi: 10.1016/j.neuroscience.2017.05.022. Epub 2017 May 19.
Pubmed: (View Article at PubMed) PMID:28528966
DOI: Full-text: DOI:10.1016/j.neuroscience.2017.05.022

Nicotinamide phosphoribosyltransferase (NAMPT) is an important neuroprotective factor in cerebral ischemia, and it has been reported that NAMPT inhibitors can aggravate neuronal injury in the acute phase. However, because it is a cytokine, NAMPT participates in many inflammatory diseases in the peripheral system, and its inhibitors have therapeutic effects. Following cerebral ischemia, the peripheral and resident inflammatory and immune cells produce many pro-inflammatory mediators in the ischemic area, which induce neuroinflammation and impair the brain. However, the effects of NAMPT inhibitors in the neuroinflammation after ischemic brain injury remain unknown. Here, we found that FK866, a potent NAMPT inhibitor, decreased the level of TNF-α, NAMPT and IL-6 in the ischemic brain tissue one day after middle-cerebral-artery occlusion and reperfusion (MCAO/R), improved neurological dysfunction, decreased infarct volume and neuronal loss, and inhibited microgliosis and astrogliosis 14days after MCAO/R. The expression of NAMPT protein was induced in Iba1-positive microglia/macrophages in the ischemia core 14days after MCAO/R. In vitro studies show that oxygen-glucose deprivation and recovery (OGD/R) activate microglia. Activated microglia increased the activity of NF-κB, increased the mRNA synthesis of TNF-α, NAMPT and IL-6, and increased the secretion of TNF-α, NAMPT and IL-6. On the other hand, NAMPT can act synergistically with other cytokines and activate microglia. FK866 strongly inhibited these changes and alleviated OGD/R-induced activation of microglia. As such, NAMPT is a crucial determinant of cellular inflammation after cerebral ischemia. NAMPT inhibitors are novel compounds to protect neuronal injury from ischemia via anti-inflammatory effects.

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CRRD Object Information
CRRD ID: 13781879
Created: 2018-08-09
Species: All species
Last Modified: 2018-08-09
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.