Motor deficits are evident in the CCI, but not mCHI or rmCHI mice.

<p><b>(A)</b> At 1 dpi, CCI mice spent significantly less active time on the beam than sham (^≠≠<i>p</i><0.01), rmCHI (^ø<i>p</i><0.05), and mCHI (^∂<i>p</i><0.05) mice. They also spent significantly less time being active on the beam at 3 dpi than sham (^≠≠<i>p</i><0.01) and mCHI (^∂<i>p</i><0.05). <b>(B)</b> At 3 dpi, the CCI mice fell off the balance beam significantly more often than the other injury groups (^ΩΩ<i>p</i><0.01). <b>(C)</b> rmCHI and mCHI mice exhibited no deficits on the foot fault task, but CCI mice had more foot faults than shams, rmCHI, and mCHI mice at 3 dpi (^≠≠≠<i>p</i><0.001, ^øøø<i>p</i><0.001, and ^∂∂∂<i>p</i><0.001, respectively), 5 dpi (^≠≠≠<i>p</i><0.001, ^øøø<i>p</i><0.001, and ^∂∂∂<i>p</i><0.001), and 7 dpi (^≠≠<i>p</i><0.01, ^øø<i>p</i><0.01, and ^∂∂∂<i>p</i><0.001). CCI mice still had significant deficits at 90+ dpi versus shams (^≠≠<i>p</i><0.01) and mCHI (^∂<i>p</i><0.05) mice. <b>(D)</b> CCI, but not mCHI or rmCHI, mice performed significantly worse on the accelerating rotarod test (5 RPM every 3 sec) at 1 and 3 dpi (^ΩΩΩ<i>p</i><0.001). These deficits were still present at 90+ dpi compared to shams (^≠≠<i>p</i><0.01) and mCHI mice (^∂∂<i>p</i><0.01).</p

Moderate CCI induced hyperactivity and spatial learning deficits.

<p><b>(A)</b> Moderate CCI mice exhibited hyperactivity in the open field, traveling a significantly greater distance at 7 dpi compared to sham (^≠≠≠<i>p</i><0.001), rmCHI (^øøø<i>p</i><0.001), and mCHI (^∂∂<i>p</i><0.01). CCI-induced hyperactivity was not observed at 90+ dpi. <b>(B)</b> At 90+ dpi, CCI mice exhibited severe deficits in the spatial water maze task, with no evidence of learning the escape platform’s location on day 1. These learning deficits persisted when the platform’s location was changed on day 2. (^≠≠<i>p</i><0.01 for CCI compared to sham, ^≠≠≠<i>p</i><0.001 for CCI compared to sham, ^ø<i>p</i><0.05 for CCI compared to rmCHI, ^øø<i>p</i><0.01 for CCI compared to rmCHI, ^∂∂<i>p</i><0.01 for CCI compared to mCHI, ^Ω<i>p</i> < .05 for mCHI compared to sham).</p

Turn bias was most evident in the mice with CCI.

<p><b>(A)</b> At 1 dpi, CCI mice made significantly fewer left turns (contralateral to the injury) on the balance beam than sham (^≠<i>p</i><0.05) and mCHI (^∂∂<i>p</i> < .01) mice. <b>(B)</b> Both rmCHI and CCI mice exhibited more turns to the right throughout balance beam testing than shams, though these results did not reach statistical significance. <b>(C)</b> CCI mice made more left-sided slips on the balance beam than other animals. These deficits were most prominent at 7 dpi compared to shams and other injury groups (^aaa<i>p</i><0.001) and persisted up to 90+ dpi (^≠≠<i>p</i><0.01 vs. sham, ^≠≠≠<i>p</i><0.001 vs. sham, ^ø<i>p</i><0.05 vs. rmCHI, ^øø<i>p</i><0.01 vs. rmCHI, ^∂<i>p</i><0.05 vs. mCHI, ^∂∂<i>p</i><0.01 vs. mCHI, ^∂∂∂<i>p</i><0.001 vs. mCHI). <b>(D)</b> In the water maze, rmCHI and CCI mice tended to swim to the left (contralateral to the injury) compared to sham and mCHI animals (*<i>p</i><0.05, **<i>p</i><0.01; mean +/- 95% CI). 95% confidence intervals show that the left turn biases in rmCHI and CCI mice are statistically significant (<i>p</i><0.05), whereas no significant turn bias is observed in the sham and mCHI mice. (The clock graphic above shows variance markings of the relative angular velocity of each injury group with each mark on the clock representing a separation of 6° in relation to 12 o’clock. Flag symbol marks zero degrees).</p

MRI assessment of severity and volumetric analysis (A) T2-weighted MRI at the level of the injury site (*) revealed no overt brain damage in sham, mCHI or rmCHI mice. In contrast, mice subjected to a moderate CCI exhibited a visible lesion within the cortex. (B) 3-D reconstruction of the T2-weighted MRI of the brain revealed no overt cortical damage in sham, mCHI or rmCHI mice. Mice subjected to a moderate CCI revealed a visible lesion (red) within the cortex. (C) MRI analysis revealed significant tissue loss in CCI mice compared to sham, mCHI and rmCHI at 90 dpi (<i>p</i> < .01).

<p>MRI assessment of severity and volumetric analysis (A) T2-weighted MRI at the level of the injury site (*) revealed no overt brain damage in sham, mCHI or rmCHI mice. In contrast, mice subjected to a moderate CCI exhibited a visible lesion within the cortex. (B) 3-D reconstruction of the T2-weighted MRI of the brain revealed no overt cortical damage in sham, mCHI or rmCHI mice. Mice subjected to a moderate CCI revealed a visible lesion (red) within the cortex. (C) MRI analysis revealed significant tissue loss in CCI mice compared to sham, mCHI and rmCHI at 90 dpi (<i>p</i> < .01).</p

Tests of affective behavior at 90 dpi suggest that TBI induces depression and increased passivity towards other mice.

<p><b>(A)</b> Depression-like behaviors were tested using the tail suspension test, in which both mCHI and rmCHI animals gave up (became immobile) more quickly than shams (**<i>p</i><0.01 and *<i>p</i><0.05, respectively), and rmCHI mice gave up more quickly than CCI animals (*<i>p</i><0.05). Interestingly, CCI mice were not different than shams. <b>(B)</b> When aggressive behavior was assessed in a social recognition test, sham, but not injured, mice engaged in more fighting with the stimulus mouse by trial 3 (*<i>p</i><0.05). rmCHI and CCI, but not mCHI, mice were more passive than shams when a new mouse was introduced on the 4^th (novel) trial, although not significantly.</p