The Preventive Effect of Ulinastatin on Blood-Brain Barrier Dysfunction in Rats with Postoperative Cognitive Dysfunction After General Anaesthesia with Isoflurane

• Published in: International journal of molecular sciences 2024-12, Vol.25 (23), p.12505
• Main Authors: Cho, Eun-Hwa, Seo, Eun-Hye, Hong, Seung-Wan, Kim, Seong-Hyop
• Format: Article
• Language: English
• Subjects: Aging; Anesthesia; Anesthesia, General - adverse effects; Anesthetics, Inhalation - adverse effects; Animals; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Cognition & reasoning; Cognition disorders; Cognitive ability; Cytokines; General anesthesia; Glycoproteins - pharmacology; Ischemia; Isoflurane; Isoflurane - adverse effects; Isoflurane - pharmacology; Male; Permeability; Postoperative Cognitive Complications - etiology; Postoperative Cognitive Complications - metabolism; Postoperative Cognitive Complications - prevention & control; Rats; Rats, Sprague-Dawley; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252312505

This study evaluated the effect of ulinastatin on blood-brain barrier (BBB) dysfunction in rats with postoperative cognitive dysfunction (POCD) following general anaesthesia with isoflurane. Specifically, we examined BBB permeability and the expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Rats in the ulinastatin group received the drug intraperitoneally (50,000 U/mL), while controls received normal saline (1 mL) administered before general anaesthesia. Isoflurane (1.5% volume) anaesthesia was induced for 2 h. Cognitive function was assessed using the Y-maze test. Two days after anaesthesia, BBB permeability was measured using Evans blue, and TIMP-1 expression was evaluated. Both groups experienced cognitive decline following anaesthesia. However, the ulinastatin group showed a more limited decrease (control group, 64.2 ± 19.3 → 30.2 ± 16.2, = 0.008; ulinastatin group, 70.0 ± 15.7 → 66.5 ± 12.0, = 0.67). The ulinastatin group showed a significantly lower permeability of the BBB (0.034 ± 0.003 µg/g in control group vs. 0.005 ± 0.002 µg/g in ulinastatin group, = 0.0001), and also showed a significantly higher value of TIMP-1 expression (5.81 ± 1.94% in control group vs. 13.97 ± 2.59% in ulinastatin group, = 0.0001). Administration of ulinastatin before general anaesthesia mitigated cognitive decline in rats with POCD, likely through the prevention of BBB dysfunction, as evidenced by the lower BBB permeability and increased TIMP-1 expression.