title: Nicotine inhibits microglial proliferation and is neuroprotective in global ischemia rats.
abstract: 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-α) and interleukin-1beta (IL-1β) 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 α-bungarotoxin, a selective α7 nicotinic acetylcholine receptor (α7 nAChR) antagonist, could prevent the inhibitory effects of nicotine on cultured microglial proliferation suggesting that nicotine inhibits the microglial proliferation in an α7 nAChR-dependent fashion. Our results suggest that nicotine inhibits the inflammation mediated by microglia via α7 nAChR and is neuroprotective against ischemic stroke, even when administered 12 h after the insult. α7 nAChR agonists may have uses as anti-ischemic compounds in humans.
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Guan
authors.forename: Xiu-Dong
authors.initials: XD
authors.lastname: Jin
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Guan
authors.forename: Hua-Cheng
authors.initials: HC
authors.lastname: Yan
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Gong
authors.forename: Shu-Ji
authors.initials: SJ
authors.lastname: Li
authors.forename: Xiong
authors.initials: X
authors.lastname: Cao
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Xing
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Gao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017208:Rats, Wistar; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine
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