• Mol Med Rep · Nov 2019

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

    • Xiao-Ping Zhang, Yu-Ru Liu, Mei Chai, Hai-Tao Yang, Guan Wang, Mei Han, and Dong-Bai Li.
    • Department of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
    • Mol Med Rep. 2019 Nov 1; 20 (5): 4226-4234.

    AbstractDamage 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.

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