Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture.
Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture.
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DOI：
10.1111/jnc.12817
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发表时间：
2014-11
影响因子：
4.7
通讯作者：
Su H
中科院分区：
文献类型：
--
作者：
Han Z;Li L;Wang L;Degos V;Maze M;Su H
中风急性期的骨折通过增加神经炎症而加重中风损伤。我们假设α-7烟碱乙酰胆碱（α-7 nAchR）激动剂的激活可减轻骨折和中风小鼠的神经炎症和氧化应激，并减轻脑损伤。将C57 BL/6 J小鼠永久性大脑中动脉闭塞（pMCAO），1天后胫骨骨折。在pMCAO后1天和2天，用0.8 mg/kg PHA 568487（PHA，α-7 nAchR特异性激动剂）、6 mg/kg Methylycaconitine（MLA，α-7 nAchR拮抗剂）或生理盐水处理小鼠。在pMCAO后3天测试行为。对神经元损伤、CD 68+、M1（促炎）和M2（抗炎）小胶质细胞/巨噬细胞、小胶质细胞/巨噬细胞中NF-κ B的磷酸化p65组分、氧化和抗氧化基因表达进行定量。与盐水处理的小鼠相比，PHA处理的小鼠在行为测试中表现更好，具有更少的凋亡神经元（NeuN+TUNEL+），更少的CD 68+和M1巨噬细胞，以及更多的M2巨噬细胞。PHA增加抗氧化基因表达，降低氧化应激和NF-κB p65磷酸化。MLA具有相反的效果。我们的数据表明，α-7 nAchR激动剂治疗可减少神经炎症和氧化应激，这与缺血性中风加胫骨骨折小鼠的脑损伤减少有关。
Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of α-7 nicotinic acetylcholine (α-7 nAchR) agonist attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle cerebral artery occlusion (pMCAO) was performed in C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0.8 mg/kg PHA568487 (PHA, α-7 nAchR-specific agonist), 6 mg/kg Methyllycaconitine (MLA, α-7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Behavior was tested 3 days after pMCAO. Neuronal injury, CD68+, M1 (pro-inflammatory) and M2 (anti-inflammatory) microglia/macrophages, phosphorylated p65 component of NF-kb in microglia/macrophages, oxidative and anti-oxidant gene expression were quantified. Compared to saline-treated mice, PHA-treated mice performed better in behavioral tests, had fewer apoptotic neurons (NeuN+TUNEL+), fewer CD68+ and M1 macrophages, and more M2 macrophages. PHA increased anti-oxidant gene expression and decreased oxidative stress and phosphorylation of NF-κb p65. MLA had the opposite effects. Our data indicate that α-7 nAchR agonist treatment reduces neuroinflammation and oxidative stress, which are associated with reduced brain injury in mice with ischemic stroke plus tibia fracture.
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影响因子：
5.2
作者：
Hayakawa K;Qiu J;Lo EH
通讯作者：
Lo EH
影响因子：
6.2
作者：
Durafourt, Bryce A.;Moore, Craig S.;Antel, Jack P.
通讯作者：
Antel, Jack P.
影响因子：
4.8
作者：
Anrather, J;Racchumi, G;Iadecola, C
通讯作者：
Iadecola, C
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG