Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture

作者：Han, Zhenying; Li, Li; Wang, Liang; Degos, Vincent; Maze, Mervyn; Su, Hua^*

来源：Journal of Neurochemistry, 2014, 131(4): 498-508.

DOI：10.1111/jnc.12817

• macrophage polarization
• middle cerebral artery occlusion
• neuroinflammation
• oxidative stress

Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of -7 nicotinic acetylcholine receptor (-7 nAchR) 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 1day later. Mice were treated with 0.8mg/kg PHA 568487 (PHA, -7 nAchR-specific agonist), 6mg/kg methyllycaconitine (-7 nAchR antagonist), or saline 1 and 2days after pMCAO. Behavior was tested 3days after pMCAO. Neuronal injury, CD68(+), M1 (pro-inflammatory) and M2 (anti-inflammatory) microglia/macrophages, phosphorylated p65 component of nuclear factor kappa b 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 nuclear factor kappa b p65. Methyllycaconitine had the opposite effects. Our data indicate that -7 nAchR agonist treatment reduces neuroinflammation and oxidative stress, which are associated with reduced brain injury in mice with ischemic stroke plus tibia fracture.

• 出版日期2014-11
• 单位天津医科大学