Anti- TNF therapy improves functional outcomes after focal cerebral ischemia. (A) Neuromuscular function presented as grip strength in grams (g), showing post-surgical weakness in both left and right front paws in saline- and XPro1595-treated mice three and five days after pMCAO compared to baseline grip strength. Etanercept-treated mice showed no loss of grip strength on the left paw, but a significant reduction in grip strength three and five days after pMCAO. BL, baseline. (P < 0.05, ***P < 0.001, ****P < 0.0001 (B) Grip strength analysis at 24 hours after pMCAO showed that asymmetry (Δ grip strength) was evident in saline-treated mice (***P <0.001, paired t-test) and, to a lesser extent, in XPro1595-treated mice (*P <0.05), but no asymmetry was observed in etanercept-treated or sham mice (six to 14 per group)(left graph). Grip strength analysis at five days showed that asymmetry was still present in saline-treated mice (*P <0.05) but not in sham, XPro1595- and etanercept-treated mice (13 to 17 per group)(right graph). (C) The horizontal rod test showed that only saline-treated mice displayed asymmetry both 24 hours (left graph) and five days (right graph) after pMCAO as saline-treated mice displayed significantly more slips on the right hind limb compared to the left limb after pMCAO (**P <0.01, paired t-test), whereas sham, XPro1595- and etanercept-treated mice did not display any asymmetry (six to 17 per group). (D) Assessment of motor function using the rotarod test showed that saline-treated mice subjected to focal cerebral ischemia did not display normal learning skills at 24 hours (left graph) and five days (right graph), whereas both XPro1595- and etanercept-treated mice displayed normal learning skills (T1 to T4) both at 24 hours and five days, comparable to sham mice (*P < 0.05, **P < 0.01, one-way ANOVA, five to six per group. g, grams; L, left; pMCAO, permanent middle cerebral artery occlusion; R, right; T, trial; sec, seconds.