Fig. 6

TBI slows the axon compound action potential velocity and amplitude. Electrophysiology recordings were used to directly test the function of axons in the corpus callosum. A Schematic of the position of the stimulating and recording electrodes for measurements of axon compound action potentials (CAP) and conduction velocity in ex vivo brain slices. B TBI reduced the speed of action potential conduction in both faster N1 wave comprised of myelinated axons and slower N2 wave comprised of unmyelinated and potentially demyelinated axons. The 7-day 4-AP treatment regimen did not restore this velocity deficit. C Representative input–output traces show the evoked N1 and N2 CAP waveforms with stimulus intensity pulses ranging from 50 to 500 µA (50 µA increments). Orange lines from CAP peaks to their projected bases indicate the amplitude of the response of fibers at a given stimulus intensity. D CAP amplitude analysis revealed a main injury effect on myelinated axons based on the reduced amplitude of only the N1 wave. N1 CAP amplitude difference was significant with post-hoc comparison for the sham versus TBI mice with 4-AP treatment. E Schematic of complementary spike waveform parameters. The width is dependent on the conduction velocity distribution among contributing axons. The time from peak to recovery represents the time for membrane repolarization among the slowest conducting axons comprising each waveform. The CAP width (F) and time from peak to recovery (G) indicated that TBI prolonged the recovery of the N2 waveform in both vehicle and 4-AP conditions. The N1 wave shape parameters were not altered by TBI or 4-AP treatment (data not shown). Abbreviations: Cing, cingulum; CC, corpus callosum; LV, lateral ventricles. B, F, G Bars represent mean ± SEM with individual data points for each mouse (n = 11–13 animals per group). D Linear effects model statistical analysis and Holm-Sidak’s multiple comparison test (*p < 0.05, **p < 0.01, ***p < 0.001). Two-way ANOVA for main effect of injury or drug with Holm-Sidak’s multiple comparisons test for post-hoc comparison of pair effects. See Fig. 1 for mouse sample numbers and Table 4 for statistical details