1.Role of meningeal γδ T cell-derived IL-17A in postoperative cognitive dysfunction in aged mice
Xiang LIU ; Xiaona TAN ; Yaozong YU ; Xuechong ZHAO ; Qiujun WANG ; Bo ZHAO
Chinese Journal of Anesthesiology 2025;45(11):1439-1444
Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.
2.Role of meningeal γδ T cell-derived IL-17A in postoperative cognitive dysfunction in aged mice
Xiang LIU ; Xiaona TAN ; Yaozong YU ; Xuechong ZHAO ; Qiujun WANG ; Bo ZHAO
Chinese Journal of Anesthesiology 2025;45(11):1439-1444
Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.

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