Dr. Yong Zhang: Modulation of Glutamate Release by Dexmedetomidine Preserves Dendritic Spines and Alleviates Cognitive Impairment in a Murine Model of Perioperative Neurocognitive Disorder

Abstract

Perioperative neurocognitive disorders (PNDs) represent a significant challenge in the perioperative setting, while the pathophysiology of PNDs remains unclear. Utilizing a murine model of abdominal surgery, we found that abnormal glutamatergic neurotransmission in the medial prefrontal cortex (mPFC) and hippocampus contributes to postoperative cognitive impairments. Increases in the frequency of miniature excitatory postsynaptic currents in both the mPFC and CA1 neurons indicate enhanced presynaptic glutamate release while having little effect on inhibitory neurotransmission. Surgery also enhances glutamate release from presynaptic terminals in the Schaffer collateral pathway. In addition, abdominal surgery increased the activation of microglia and astrocytes, elevated central inflammatory markers, and reduced excitatory amino-acid transporter-2 expression. Dexmedetomidine significantly mitigates the postoperative cognitive deficits by reducing inflammation and preserving neuronal structural complexity and dendritic spine stability, likely through inhibiting glutamate release and enhancing its reuptake. These findings advance our understanding of the etiology of PNDs and provide hints for potential intervention.

Original Link: https://link.springer.com/article/10.1007/s12264-025-01518-w