Gastrodin alleviates perioperative neurocognitive dysfunction of aged mice by suppressing neuroinflammation

Perioperative neurocognitive disorder (PND) is a common complication of elderly patients after surgery and lacks effective prevention and treatment measures. We investigated the effect and mechanism of gastrodin (GAS), a natural plant ingredient, on postoperative cognition induced by laparotomy in aged mice. Male aged (18 months) mice were subjected to lapamtomy and orally treated with GAS (25, 50, and 100 mg/kg) 3 weeks before surgery and 1 week after surgery. In addition, some male aged (18 months) mice were subjected to viral vector or GSK-3 beta expression virus injection followed by laparotomy with or without 100 mg/kg GAS treatment. GAS improved learning and memory in aged mice after surgery. Surgery increased the levels of pro-inflammatory factors (TNF-alpha, IL-1 beta and IL-6) and decreased the level of an anti-inflammatory factor (IL-10) in the mouse hippocampus, and these changes were reversed by GAS treatment. GAS also suppressed the activation of microglia. GAS inhibited the phosphorylation of GSK-3 beta and Tau. Furthermore, surgery induced more serious cognitive dysfunction, inflammatory factors, activation of microglia, and phosphorylation of GSK-3 beta and Tau in GSK-3 beta overexpressing aged mice. The improvement of learning and memory, the reduction of inflammation and microglia activation, and the suppression of GSK-3 beta and Tau phosphorylation by GAS were prevented when GSK-3 beta was overexpressed in aged mice subjected to surgery. Our finding suggested that GAS exerts neuropmtective effects in aged mice subjected to lapamtomy by suppressing neuroinflammation and GSK-3 beta and Tau phosphorylation. Thus, these findings suggest that GAS may be a promising agent for PND.