Mechanism of Aquaporin-4 Up-Regulation After Traumatic Brain Injury and Preventative Action of Astragalus Polysaccharides in Mice

Abstract

Here, we aimed to clarify the anti-inflammatory function of Astragalus Polysaccharides (APS), a chemical compound derived from Astragalus membranaceus, and the action of AQP4 on brain injury. We hypothesized that APS could improve the traumatic brain injury (TBI) outcome via inhibiting expression of AQP4 in astrocytes. The present study elucidated that AQP4 was up-regulated and was effectively blocked by APS in mice with severe controlled cortical impact (CCI). Pre-treatment with APS effectively inhibited the up-regulation of AQP4 and diminished the neurological deficits in mice. Additionally, primary astrocytes treated with mechanically-injured astrocyte supernatant, to mimic TBI in vitro, showed a significant up-regulation in swelling. We confirmed various signal molecules (NF-ĸB, MAPKs, and ERK) to have a role in astrocyte swelling, after activation in trauma, and to be involved in the up-regulation of AQP4. These signal molecules also significantly decreased with APS treatment. In conclusion, our study suggests that APS attenuated neurological deficits and brain edema by decreasing AQP4 up-regulation in astrocytes following TBI in mice, via reducing NF-ĸB, MAPKs, and the ERK signal molecules.