Inflammation plays a central role in neonatal brain injury. During brain inflammation the resident macrophages of the brain, the microglia cells, are rapidly activated. In the periphery,α7 nicotinic acetylcholine receptors (α7R) present on macrophages can regulate inflammation by suppressing cytokine release. In the current study we investigatedα7R expression in neonatal mice after hypoxia-ischemia (HI). We further examined possible anti-inflammatory role ofα7R stimulationin vitroand microglia polarization afterα7R agonist treatment. Real-time PCR analysis showed a 33% reduction inα7R expression 72 h after HI. Stimulation of primary microglial cells with LPS in combination with increasing doses of the selectiveα7R agonist AR-R 17779 significantly attenuated TNFαrelease and increasedα7R transcript in microglial cells. Gene expression of M1 markers CD86 and iNOS, as well as M2 marker CD206 was not influenced by LPS and/orα7R agonist treatment. Further, Mox markers heme oxygenase (Hmox1) and sulforedoxin-1 (Srx1) were significantly increased, suggesting a polarization towards the Mox phenotype afterα7R stimulation. Thus, our data suggest a role for theα7R also in the neonatal brain and support the anti-inflammatory role ofα7R in microglia, suggesting thatα7R stimulation could enhance the polarization towards a reparative Mox phenotype.
Role of anti-inflammatory compounds in human immunodeficiency virus-1 glycoprotein120-mediated brain inflammation
