Catalpol Alleviates Isoflurane-Induced Hippocampal Learning and Memory Dysfunction and Neuropathological Changes in Aged Mice

Abstract

Introduction: Isoflurane-associated perioperative neurocognitive disorders (PNDs) is a common complication that occurs commonly in elderly patients characterized by deterioration of hippocampus-dependent cognitive function. Mounting evidence has shown that hippocampal impairment and inflammatory processes are implicated in the pathogenesis of PNDs. Catalpol has been suggested to play a role in the modulation of neuroprotection and neurotransmission. Therefore, we surmised that catalpol may play a similar role during isoflurane-induced PNDs. Methods: In our current study, aged mice were exposed to isoflurane to develop a mouse model of PNDs and preconditioned with catalpol for 2 weeks before modeling. Three weeks after isoflurane exposure, behavioral, histological, biochemical, electrophysiological, and immunofluorescent assays were performed. Results: Our results showed that catalpol preadministration significantly alleviated cognitive impairment in the Morris water maze, novel object recognition, and Y-maze behavioral tests. Neuropathological analyses showed that catalpol preadministration reduced the loss of neurons and synapses; in line with this, it is revealed that hippocampal synaptic plasticity was restored. Mechanistically, catalpol preadministration suppressed the activation of microglia and decreased the expression of NLRP3 inflammasome. Conclusion: Our results indicate that catalpol preadministration could effectively alleviate cognitive impairment and neuropathological damage in isoflurane-exposed aged mice with its neuroprotective effects via modulation of the NLRP3 inflammatory pathway. Furthermore, the NLRP3 inflammatory pathway was revealed to be involved in these effects.