Measurements of rat behavior during open field, passive place avoidance and active place avoidance.

<p>Rats received either sham- or moderate-CCI. Beginning one hour after surgery the rats received either saline, cyclosporine (CYCLO) simvastatin (SIM), progesterone (PROG), minocycline (MINO), n-acetyl cysteine (NAC) or MINO plus NAC. Seven days later all groups were tested on the hierarchy of three behavioral tasks. In the open field test, there was no effect of treatment on total distance traveled (F_7,40 = 0.40, p>0.8). In passive place avoidance, there was no effect of treatment on either average distance over 4 trials or shock zone entrances (total distance, F_7,40 = 0.67, p>0.6; entrances, F_7,40 = 0.48, p>0.8). In massed active place avoidance testing on the 6^th trial of the first day, there was no effect of treatment on speed (F_7,40 = 0.44, p>0.8) or linearity (F_7,40 = 0.25, p>0.9)). The number of shocks per entrance in CCI-saline treated rats was not changed by the drugs individually or in combination (F_7,40 = 0.39, p>0.6). In contrast, there was a significant treatment effect with MINO or MINO plus NAC significantly improved time to first entrance (F_4,35 = 26.7, p<0.0001; **p<0.001, *p<0.05; post-hoc test).</p

MINO or MINO plus NAC prevented IL-1β formation when administered before moderate CCI.

<p>Rats were dosed with saline, MINO, NAC or both drugs 3 hours prior to sham- or moderate CCI. The rats were sacrificed one hour after surgery; and IL-1β and tubulin levels were assayed from protein extracts prepared from hippocampus. <b>Panel A</b>, Representative Il-1β and tubulin immunoblot analysis, <b>Panel B</b>, Summary of immunoblot analysis.</p

MINO plus NAC prevented myelin loss.

<p><b>Panel A</b>, Schematic of the regions of interest (ROIs) from a coronal section located −3.36 mm from Bregma <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012490#pone.0012490-Paxinos1" target="_blank">[40]</a>. The ROIs were: corpus callosum (A), dorsal hippocampal commissure (B), stratum radiatum (C), fimbria (D), internal capsule (E), fornix (F), mammilothalamic tract (G). <b>Panel B</b>, Representative images of corpus callosum and dorsal hippocampal commissure stained with luxol fast blue. B1, Sham-CCI-saline; B2 CCI-saline; B3, CCI-MINO plus NAC. The scale bar corresponds to 100µm.</p

MINO provided a modest improvement of active place avoidance following moderate CCI.

<p>The total number of entrances into the shock zone was assayed in the 6 trials of active place avoidance training.</p

MINO plus NAC synergistically improved active place avoidance after massed training.

<p>Panel A, Rats received either CCI or sham-CCI. One hour, one or days later the sham-injured the CCI-injured rats were divided into 4 groups; one group received saline treatment. The remaining CCI-injured rats received either MINO or NAC alone, or the combination of MINO plus NAC. Saline or drug treatments were administered 1 hour, 1 day and 2 days after injury. Rats received active place avoidance training 8 and 9 days after injury. On the 8th and 9th day following CCI, the number of shock zone entrances was measured. <b>Panel B</b>, Representative tracks of rats in the sham-CCI-saline, CCI-saline or CCI-MINO plus NAC groups on the 6^th trial on the first day of active avoidance training. Red lines indicate the boundaries of the shock zone and the red circles indicate the location were a rat received a shock. <b>Panel C</b>, Summary of the number of shock zone entrances over the two days of active place avoidance.</p