Silencing SP1 Alleviated Sevoflurane-Induced POCD Development via Cholinergic Anti-inflammatory Pathway

Abstract

Postoperative cognitive dysfunction (POCD) is a common complication induced by anesthesia or surgery, which affects the concentration, cognition and memory of patients. Sevoflurane, a clinical anesthetic, could stimulate neuro-inflammation and lead to POCD. Recent studies found that specificity protein 1 (SP1) participates in the development of neurological diseases. Our study aims to elucidate the role of SP1 in sevoflurane-induced POCD pathogenesis. We anesthetized Sprague-Dawley rats and treated the primary hippocampal neurons with sevoflurane to construct the in vivo and in vitro POCD models. Besides, the expression and regulatory mechanism of SP1 in the pathogenesis of POCD were explored. According to the results, sevoflurane anesthesia impaired the cognitive functions of rat, significantly elevated SP1 expression and inactivated the cholinergic anti-inflammatory pathway (CAP) both in vivo and in vitro. Moreover, the sevoflurane-treated rats and neurons also exhibited obvious inflammatory responses and enhanced apoptosis. Loss-of-function assay indicated that SP1 knockdown rescued the deactivation of CAP and alleviated the sevoflurane-induced neuro-inflammation and apoptosis in rat hippocampus. Generally, our study documented that the sevoflurane-induced SP1 up-regulation affected the activation of CAP, leading to the aggravated neuro-inflammation and apoptosis. This may provide a novel sight for POCD therapy.

Keywords: Cholinergic anti-inflammatory pathway; Inflammation; Postoperative cognitive dysfunction; Sevoflurane; Specificity protein 1.