Frontiers in aging neuroscience
Camk2d upregulation is associated with postoperative cognitive dysfunction in aged rats: pharmacological inhibition of CaMKII attenuates hippocampal neuroinflammation and neuronal apoptosis
By Wei K, Fan S, Zhao Y and 4 others.
Abstract
Background
Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients after major surgery. It delays postoperative recovery and increases the risk of neurodegenerative disorders. CaMKIIδ is a key calcium-signaling regulator of neuronal survival and neuroinflammation, yet its functional role in POCD remains poorly understood. This study aimed to identify injury-inducible calcium-signaling genes and to characterize the association of Camk2d, the gene encoding CaMKIIδ, with POCD progression in aged rats.
Methods
A POCD model was established in aged rats by sevoflurane anesthesia combined with splenectomy. Cognitive function was evaluated with the Morris water maze (MWM) and Y-maze tests. Hippocampal transcriptome profiling was performed using RNA sequencing and weighted gene co-expression network analysis (WGCNA). Key molecular and pathological alterations were validated by RT-qPCR, Western blotting, ELISA, and histological staining, and the pan-CaMKII inhibitor KN-93 was administered for functional validation. Serum inflammatory cytokines were measured in parallel to characterize peripheral-to-central inflammatory coupling.