Fig. 10
Cell cycle inhibition by CR8 improves functional outcomes following TBI plus hypobaria. a–d Cognitive assessment of CR8 treatment using the Morris water maze (MWM). The TBI + CR8 + HB group showed significant improvements in spatial learning deficits in comparison to the TBI + vehicle + HB group following prolonged hypobaria exposure at 6 h after TBI. The swimming patterns during all trials on the fourth day of the acquisition phase were analyzed to assess the search strategies utilized by the animals to locate the hidden platform. A chi-square analysis was used to compare strategies between groups and was found to be significant (p < 0.0001, χ 2 = 57.79, df = 4). Animals in the vehicle + HB group were less efficient in their search strategy while attempting to locate the hidden platform. CR8 treatment increased the percentage of trials in which a spatial search strategy was utilized. Spatial memory was assessed using the MWM probe trial on day 18 after HB by examining the number of entries into the target quadrant. CR8 treatment increased the number of target quadrant entries in comparison to the TBI + Veh + HB group indicating a reduction in retention memory deficits in the probe trial. Swim speeds did not differ across groups (p = 0.4382). e Nonspatial memory was assessed using the novel object recognition test on post-HB day 21. Animals showed an equal preference for the two identical objects during the training phase. CR8 treatment significantly increased the discrimination index in comparison to the TBI + Veh + HB group indicating an improvement in nonspatial memory. f Depressive-like behaviors were assessed using the forced swim test. CR8 treatment did not significantly reduce the depressive-like behavior caused by TBI plus HB. N = 16 (sham), 14 (TBI + Veh + HB), 15 (TBI + CR8 + HB). *p < 0.05, **p < 0.01, TBI + CR8 + HB vs. TBI + Veh + HB