FIG. 4.
Early systemic administration of PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide) improves sensorimotor function but not cognitive performance after traumatic brain injury (TBI). (A) Fine motor coordination deficits were quantified using the beam walk test. Hind-limb foot placement was recorded and the number of mistakes (foot faults) was recorded from 50 steps. TBI induced significant impairment in motor outcomes at all time points (***p<0.001 vs. sham). There was a statistically significant “post-injury day X groups” interaction (F(8,125)=6.541, p<0.001). Systemic administration of PJ34 starting at 3 h post-injury significantly improved fine motor coordination at 7, 14, and 21 days (+++p<0.001 vs. vehicle) post-TBI. Analysis by repeated measures one-way analysis of variance (ANOVA), followed by multiple pair-wise comparisons using the Student Newman-Keuls post-hoc test. Mean±standard error of the mean (SEM). n=12 TBI groups, n=5 sham-injured group. (B) Systemic administration of PJ34 starting at 3 h post-injury did not improve cognitive performance in the Morris water maze (MWM) test after TBI. Spatial learning and memory was assessed using the MWM test. The factors of “post-injury days” and “groups” were not statistically significant. TBI induced significant cognitive impairments at post-injury days 14, 15, 16, and 17 (*p<0.05 vs. sham, ***p<0.001 vs. sham). PJ34-treated TBI mice demonstrated a latency to locate the submerged platform that was not significantly different compared with vehicle-treated TBI mice. (C) In the probe trial, vehicle- and/or PJ34-treated TBI mice spent significantly less time in the target quadrant compared with sham-injured mice (*p<0.05). No significant differences were observed between vehicle- and PJ34-treated TBI mice. (D) No significant differences in swim speed were observed between sham, vehicle-treated, and PJ34-treated TBI mice. Analysis by repeated measures one-way ANOVA (A, B, D) and one-way ANOVA (C), followed by multiple pairwise comparisons using the Student Newman-Keuls post-hoc test. Mean±SEM (n=12 TBI groups, n=5 sham-injured groups).