P (n = eight evaluation of variance at POD 7 with post hoc Tukey test. CCI fumagillin group at POD 14; n = six for CCI group at POD 14 and CCI fumagillingroup at POD 7). Moreover, the effect of fumagillin in suppressing CCIupregulated 3.8. Fumagillin Intrathecal Administration tended to be stronger Astrocyte Activation Pyrazosulfuron-ethyl In Vitro albeit TNF and IL6 concentrations at POD 7Attenuates CCIInduced than that at POD 14,in the Ipsilateral Lumbar KU-0060648 Technical Information spinal Cord not statistically significant (Figure 7B,C). Unexpectedly, fumagillin considerably improved IL10CCI markedly upregulated GFAP immunoreactivities (147.9 14 compared to 4.8, pof levels at POD 7 and 14 in comparison to that of CCI rats at POD 20.6 vs. 110.3 that = the manage group1.7 vs. 1fold, 5.two 0.001; Figure eight). GFAP=expression was decreased in 0.0076, and 140.4 12.7 vs. 114.6 pg/100 proteins, p 0.0332). The improved IL10 the CCI fumagillin group in comparison to that from the CCI group (0.6 vs. 1.7fold, p on the other hand, production induced by fumagillin seemed greater at POD 7 than that at POD 14; = 0.00278) but not statistically substantial compared to that of control In summary, fumagillin moduthe distinction was not statistically important (Figure 7D).groups (0.6 vs. 1fold, p = 0.232) (n = 3CCIinduced neuroinflammation by demonstrate that intrathecal administration of lates per group; Figure 8A,B). These information enhancing IL10 amounts and inhibiting the fumagillin of TNF abolishes astrocyte activation in levels. productioneffectively and IL6 without the need of affecting IL1the ipsilateral lumbar spinal cord in CCIinduced neuropathic discomfort.Figure 7. Cont.Biomedicines 2021, 9,16 ofBiomedicines 2021, 9, x FOR PEER REVIEW16 of3.8. Fumagillin Intrathecal Administration Attenuates CCIInduced Astrocyte Activation within the Ipsilateral Lumbar Spinal CordFigure 7. Effects of intrathecal administration of fumagillin on cytokine levels within the spinal cord of CCI ratswas decreased in Figure 7. Effects of intrathecal administration of fumagillin on cytokine levels within the spinal cord of CCI rats 7 and 14 days the control group (1.7 vs. 1fold, p 0.001; Figure 8). GFAP expression 7 and 14 days following CCI. (A) interleukin11 (IL1), tumor necrosis element (TNF), (C) ), (C) IL6, IL10 levels within the spinal following CCI. (A) interleukin (IL1), (B) (B) tumor necrosis issue that ofIL6, and (D) and (D) IL10 1.7fold, p = the CCI fumagillin group in comparison with (TNF the CCI group (0.six vs. levels in cord of handle rats (n = eight) and chronic constriction injury (CCI) rats at postoperative day (POD) 7 (n = 8), CCI fumagillin the spinal cord of manage rats (n = 8) and chronic constriction injury comparedat postof handle day (POD) 7 (n = 1fold, 0.00278) but not statistically important (CCI) rats to that operative groups (0.6 vs. 8), rats at POD 7 (n = 6), CCI rats at POD 14 (n = six), and CCI fumagillin rats at POD 14 (n = eight). Information are represented as signifies CCI fumagillin rats at POD 7 (n = 6), CCI rats at POD 14 (n = 6), and CCI fumagillin rats at POD 14 (n = 8). Information adminp = 0.232) (n = three per group; Figure 8A,B). These p 0.05 compared that intrathecal are normal error of implies (SEMs), p 0.05 compared with all the manage group; # data demonstratewith the CCI group at represented as indicates typical error of implies with post p 0.05 compared with the manage group; # p ipsilateralsign istration of fumagillin properly abolishes The “” sign signifies the absence and “” lumbar POD 7; oneway analysis of variance (ANOVA) (SEMs), hoc Tukey test. astrocyte acti.