AdipoRon Attenuates Neuroinflammation After Intracerebral Hemorrhage Through AdipoR1-AMPK Pathway. (1st August 2019)

• Record Type: Journal Article
• Authors: Zheng, Jingwei; Sun, Zeyu; Liang, Feng; Xu, Weilin; Lu, Jianan; Shi, Ligen; Shao, Anwen; Yu, Jun; Zhang, Jianmin
• Is Part Of: Neuroscience. Volume 412(2019)
• Page Start: 116
• Page End: 130
• Publication Date: 2019-08-01
• Subjects: ICH Intracerebral hemorrhage -- SBI secondary brain injury -- ROS reactive oxygen species -- BBB blood brain barrier -- AMPK AMP-activated protein kinase -- OxyHB oxyhemoglobin -- Sirt3 sirtuin3 -- SOD2 superoxide dismutase 2 -- FBS fetal bovine serum -- PBS phosphate buffered saline -- PVDF polyvinylidene fluoride -- MRI Magnetic Resonance Imaging -- NSCs neural stem cells -- CNS central nervous system; ICH -- inflammation -- microglia -- adipoRon; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.05.060
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: Neuroinflammation is considered to be a critical component in the pathological process after intracerebral hemorrhage (ICH). Microglia are the foremost and earliest inflammatory cells participating in the pathological process of ICH. AdipoRon is the agonist of AdipoR1 (Adiponectin receptor 1), which enhances P-AMPK (phosphorylated AMP-activated protein kinase) activation. The activated AMPK facilitates microglia/macrophage polarization by driving the cell state from pro-inflammatory M1 state to anti-inflammatory M2 state. The study aims to investigate the role of AdipoRon in microglial polarization and neuroprotection after ICH. The experimental ICH model was established by autologous blood injection, and the treated group was done additionally by intraperitoneal injection of drugs. Flow cytometry analysis and immunofluorescence staining were performed to quantify the ratio of M1 to M2 phenotype microglia in mice. The present study indicated that AdipoRon could ameliorate neurological deficits in mice after ICH. Flow cytometric analysis demonstrated that the proportion of CD206 + cells to CD45 +low CD11b + cells (microglia isolated from the brain tissue of mice) was increased after AdipoRon treatment. AdipoR1 siRNA and AMPK inhibitor could reverse the positive effects of AdipoRon. AdipoR1 and P-AMPK expression was also significantly increased after AdipoRon treatment. The in vitro experiment showed that AdipoRon not only directly inhibited neuronal ROS overproduction, but also indirectly decreased the neuronal death in a transwell co-culture system. In summary, AdipoRon protects against ICH induced injury through promoting M2a microglia polarization and reducing neuronal death. These effects of AdipoRon rely on the activation of AdipoR1-AMPK signaling pathway. Highlights: AdipoRon protects against ICH induced brain injury in mice. AdipoRon promotes M2 microglial polarization whereas inhibits M1 microglial polarization through AdipoR1-AMPK pathway. AdipoRon ameliorates ICH induced neuronal damage in vitro via both direct and indirect route.