Nicotine Inhibits Microglial Proliferation and Is Neuroprotective in Global Ischemia Rats

作者：Guan, Yan-Zhong; Jin, Xiu-Dong; Guan, Li-Xin; Yan, Hua-Cheng; Wang, Pu; Gong, Zhi; Li, Shu-Ji; Cao, Xiong; Xing, Yan-Li; Gao, Tian-Ming^*

来源：Molecular Neurobiology, 2015, 51(3): 1480-1488.

DOI：10.1007/s12035-014-8825-3

• Nicotine
• Microglia
• Proliferation
• Stroke
• Neuronal death

Ischemic injury in rodent models reliably leads to the activation of microglia, which might play a detrimental role in neuronal survival. Our preliminary studies suggest that nicotine plays a potential role in decreasing the numbers of cultured microglia in vitro. In the present study, we found treatment with nicotine 2, 6, and 12 h after ischemia for 7 days significantly increased the survival of CA1 pyramidal neurons in ischemia/reperfusion rats. This effect was accompanied by a significant reduction in the increase of microglia rather than astrocytes, as well as a significant reduction of enhanced expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1 beta) in CA1 induced by ischemia/reperfusion. Nicotine inhibits microglial proliferation in primary cultures with and without the stimulation of granulocyte-macrophage colony-stimulating factor (GM-CSF). Pre-treatment with alpha-bungarotoxin, a selective alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR) antagonist, could prevent the inhibitory effects of nicotine on cultured microglial proliferation suggesting that nicotine inhibits the microglial proliferation in an alpha 7 nAChR-dependent fashion. Our results suggest that nicotine inhibits the inflammation mediated by microglia via alpha 7 nAChR and is neuroprotective against ischemic stroke, even when administered 12 h after the insult. alpha 7 nAChR agonists may have uses as anti-ischemic compounds in humans.

• 出版日期2015-6
• 单位牡丹江医学院; 南方医科大学