Agmatine attenuates postoperative cognitive dysfunction in rats through reducing neuroinflammation

Objective To observe the effects of agmatine on neuroinflammation and cognitive function in adult rats after surgery. Methods SD rats were randomly divided into five groups: a normal saline (NS) group, a NS+ surgery under anesthesia (NS+Sur) group, and low-, medium- and high-dose agmatine+ surgery under anesthesia (AGM 20 mg/kg+Sur, AGM 40 mg/kg+Sur, and AGM 80 mg/kg+Sur) groups. Each group underwent splenectomy with sevoflurane anesthesia. Their learning and memory abilities were tested by Morris maze. Then, three days after surgery, the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in the hippocampus were detected by ELISA. The amounts of p-nuclear factor (p-NF)-κB p65 in the hippocampus, and ZO-1 and Occ were detected by Western blot. The expression of GFAP in hippocampal astrocytes was detected by immunofluorescence.The permeability of the blood-brain barrier in rats was detected by Evans blue. Results Three days after anesthesia, compared with the NS group, the NS+Sur group showed significantly decreased cognitive function (P<0.01), increased levels of p-NF -κB P65, IL-1β, IL-6, TNF-α and GFAP in the hippocampus, significantly decreased expression of ZO-1 and Occ in brain microvessels, and significantly increased exudation of Evans blue in brain tissue (P<0.01). Compared with the NS+Sur group, the AGM80+Sur group showed significantly enhanced cognitive function (P<0.05), reduced levels of p-NF-κB P65, IL-1β, IL-6, TNF-α and GFAP in the hippocampus, significantly increased expression of ZO-1 and Occ in brain microvessels, and significantly depresssed exudation of Evans blue in brain tissue (P<0.01). Conclusions Agmatine can reduce neural inflammation, decrease blood-brain barrier permeability and improve cognitive dysfunction.