Tau hyperphosphorylation: a downstream effector of isoflurane-induced neuroinflammation in aged rodents

Postoperative cognitive dysfunction (POCD) is a severe neurological sequela after anesthesia and surgery. Multiple risk factors, such as advanced age and anesthesia duration, relevant to POCD have been made out, although the pathophysiological mechanisms of this complication need to be further elucidated. To date, there is a substantial body of evidence implicating that neuroinflammatory cytokines and the subsequent neuroinflammatory response contribute to the cognitive impairment in aged rodents exposed to isoflurane, a commonly used general anesthetic. Interestingly, this cognitive disorder is mitigated by anti-inflammatory agents even 14 days after isoflurane exposure. In addition, isoflurane-induced upregulation of neuroinflammatory cytokines is only limited within 48 h. So a first possibility to consider is a downstream effector of isoflurane-induced neuroinflammatory cytokines which contributes to the long-lasting cognitive dysfunction. In Alzheimer's disease (AD) models, proinflammatory cytokines can induce tau hyperphosphorylation which is associated with synaptic abnormality and further cognitive impairment. It is unknown whether isoflurane-induced neuroinflammatory cytokines can trigger tau hyperphosphorylation. Taken together, we hypothesize that tau hyperphosphorylation is a downstream target of isoflurane-induced neuroinflammatory response and thus bridges the isoflurane-induced relatively transient neuroinflammatory process to the long-term cognitive impairment.