High‑fat treatment prevents postoperative cognitive dysfunction in a hyperlipidemia model by protecting the blood‑brain barrier via Mfsd2a‑related signaling

Abstract

Damage to the blood-brain barrier (BBB) resulting from systemic inflammation caused by surgical trauma is associated with cognitive dysfunction, and individuals with hyperlipidemia are more sensitive to such impairment. The present study was designed to ascertain whether dexmedetomidine (Dex) treatment could reduce the incidence of cognitive dysfunction following surgery in a hyperlipidemia model. Hyperlipidemia was induced in Sprague-Dawley rats (male, 6–7 months old) by consuming a high-fat diet, and rats were divided into three groups (n=10 each) and underwent: exploratory laparotomy to introduce surgical trauma (surgery group), laparotomy and Dex treatment (surgery+Dex group), or sham surgery (sham group). Learning, memory and exploration behavior were assessed using the Morris water maze. Concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, were determined by enzyme-linked immunosorbent assay. BBB permeability was assessed by Evans blue staining. Relative major facilitator superfamily domain-containing protein 2 (Mfsd2a) mRNA expression was determined by quantitative PCR. In the Morris water maze test, the time and distance ratio for the surgery group was significantly lower than those of the sham and surgery+Dex groups (P<0.05). In addition, the TNF-α concentrations in the sham and surgery+Dex groups were lower than that in the surgery group (P<0.05 on days 1 and 3). Evans Blue staining was increased in the surgery group on day 1 (P<0.01). Mfsd2a mRNA expression was higher in the sham and surgery+Dex groups compared with that noted in the surgery group (P<0.05). In conclusion, Dex treatment decreased the incidence of cognitive dysfunction following surgical trauma in a hyperlipidemia rat model. We demonstrated that Dex stabilized BBB integrity through increased Mfsd2a gene expression.

The Influence of Different Dexmedetomidine Doses on Cognitive Function at Early Period of Patients Undergoing Laparoscopic Extensive Total Hysterectomy

“…The long operation duration is coupled with factors such as postural changes of laparoscopic operation, traumatic stress, and CO 2 pneumoperitoneum. It triggers the body's sympathetic nerve excitement, increases the release of catecholamines, and causes significant stress and inflammation reactions [ 15 , 16 ]. The systemic inflammatory response that occurs under surgical trauma stress may play an essential role in the occurrence of POCD [ 17 ].…”

Update on the Mechanism and Treatment of Sevoflurane-Induced Postoperative Cognitive Dysfunction

“…Studies have shown that Dex can stabilize the integrity of the blood-brain barrier and reduce apoptosis. These protective effects may be mediated by reducing the activation of the NF-κB and NLRP3 inflammasome pathways ( Zhang X.P. et al, 2019 ).…”

Delirium risk factors in hospitalized patient: a comprehensive evaluation of underlying diseases and medications in different wards of a large Urban Hospital Center in Iran

“…The number of patients with malignancy involved in this study was not enough to evaluate the specific subtypes of malignancies for delirium, but according to previous studies, the patients with primary or secondary CNS tumors, cancers with paraneoplastic neurological features and terminal cancers are at higher risks to develop delirium [ 31 , 32 ]; however, taking the chemotherapy medications that were reported as a predisposing factor for delirium in previous studies, were not associated with higher risks of delirium in our study. Because of the insufficient number of patients with hyperlipidemia and liver disease, we were not able to analyze these two variables; according to previous studies, hyperlipidemia plays a protective role by strengthening the blood-brain barrier, and liver diseases by disturbing plasma metabolites and electrolytes are risk factors for delirium [ 33 – 35 ].…”