Pleiotrophin Potentiates Sevoflurane Anesthesia-induced Learning Deficits in Mice

Postoperative cognitive dysfunction (POCD) is a major postoperative neurological complication in children and the elderly. However, the detailed mechanisms underlying this process remain unclear. This study aims to investigate the effect of pleiotrophin on sevoflurane-induced neuroinflammation and cognitive impairment. The novel object recognition test was performed to evaluate the cognitive and motor function of aged C57BL/6 (wild-type, WT) and pleiotrophin-knockout mice treated with sevoflurane. Small molecule inhibitors targeting receptor protein tyrosine Phosphatase (RPTP) β/ζ, a pleiotrophin receptor, were used to ameliorate cognitive dysfunction. Sevoflurane treatment induced cognitive dysfunction and motor impairment in aged WT mice. Sevoflurane anesthesia induced the upregulation of certain inflammatory cytokines. Pleiotrophin knockout ameliorated the sevoflurane-induced cognitive dysfunction and motor impairment in vivo. Treatment with small molecule inhibitors targeting RPTP β/ζ inhibited sevoflurane-induced neuroinflammation. In summary, pleiotrophin was shown to potentiate sevoflurane anesthesia-induced cognitive dysfunction and learning deficits in mice.