Fig. 3
Novel TNF-R1 inhibitors modulated post-traumatic sleep and improved functional outcome measures following TBI. Following preliminary sleep screening, a second cohort of mice was tested for functional outcome following administration of low-dose (2 mg/kg) compounds given immediately following injury or sham procedure. a The rotarod was used to test motor function. There was a significant effect of time after injury (F3,102 = 9.612, p < 0.0001) and group effect on the latency to fall from the rotarod (F3,34 = 6.646, p = 0.0012). SGT attenuated motor deficits by 3 days post-injury (DPI). b There was a significant time effect (F1,34 = 17.14, p = 0.0002) and treatment effect (F3,34 = 8.450, p = 0.0002). Sidak’s post hoc analysis indicated SGT led to a significant improvement at 7 DPI compared to 1 DPI. c Neurological deficits were measured by a modified Neurological Severity Score (NSS). Median NSS scores differed among groups with a treatment effect (\( {\chi}_3^2 \) = 32.669; p < 0.001) and time effect (\( {\chi}_3^2 \) = 10.178; p = 0.021). At 3 and 5 DPI, SGT attenuated neurological deficits. d All injured groups showed improvement on the NSS task by 7 DPI. e Cognitive impairment was measured by novel object recognition (NOR). Differences in time spent exploring the novel versus familiar object revealed a significant difference between investigation times among sham (t11 = 2.686, p = 0.0212) and SGT-treated brain-injured mice (t9 = 2.277, p = 0.0488), indicating recall of the familiar object. Vehicle-treated brain-injured mice (t6 = 1.371, p = 0.2195) and C7 treated brain-injured mice (t8 = 1.259, p = 0.2435) spent similar times investigating both objects. f There were no significant differences in discrimination indices between groups (F3,34 = 0.2276, p = 0.8766). g TBI led to increased sleep during the first light cycle (F3,25) = 3.933, p = 0.0199). h TBI did not alter sleep during the transition from light to dark cycle (F3,25 = 0.5272, p = 0.6677). i There was an overall effect on cumulative sleep during the light cycle (F3,25) = 3.233, p = 0.0393) mice slept similarly during the dark cycle (F3,25 = 0.8089, p = 0.5009). Behavior groups: sham n = 12, vehicle-treated n = 7, C7-treated n = 9, SGT-treated n = 10. Sleep groups: sham n = 9, vehicle-treated n = 5, C7-treated n = 6, SGT-treated n = 9