The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity.

This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype.

The Effect of Ketamine on Endoplasmic Reticulum Stress in Rats with Neuropathic Pain.

This study aimed to investigate the effects of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on endoplasmic reticulum (ER) stress in rats with neuropathic pain (NP). NP was induced in rats through ligation and transection of the sciatic nerve. After confirmation of NP, the animals were randomly divided into ketamine and control groups. The ketamine group was administered 50 mg/kg of ketamine at 15, 18, and 21 days after surgery. The expression of NMDA receptor subtype 2B (NR2B) and ER stress markers in the spinal cord (L5) was evaluated. The ipsilateral side of the surgery in the ketamine group was less sensitive to mechanical and cold stimulations. The expression of NR2B on the ipsilateral side was significantly lower in the ketamine group than in the control group (18.93 ± 1.40% vs. 31.08 ± 0.74%, p < 0.05). All markers for ER stress on the ipsilateral side of the surgery in both groups had higher expression than those on the contralateral side. The expression of activating transcription factor-6 (ATF-6) on the ipsilateral side was significantly lower in the ketamine group than in the control group (p < 0.05). Systemic administration of ketamine inhibited the expression of NMDA receptors and improved NP symptoms. Among the markers of ER stress, the therapeutic effect of ketamine is associated with the inhibition of ATF-6 expression.