Post-ischemia IH intervention induced hippocampal c-Fos expression and MAPK phosphorylation.

<p>(A) Immunoblotting was used to detect hippocampal pMAPK, MAPK, and c-Fos expression. (B) Quantification of immunoblotting results. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p<</i>0.001, compared to the MCAOIH group. ††<i>p</i><0.01, †††<i>p<</i>0.001, compared to the NorIH group.</p

Reversal of spatial learning and memory impairments in ischemic rats following IH intervention.

<p>(A) Experimental design. (B) Escape latencies observed during 7 consecutive days of training on the MWM. (C) Swimming distances seen during 7 consecutive days of training on the MWM. (D, left) Time spent in the target quadrant (zone IV) during the MWM probe test. (D, right) Swim paths taken by a representative rat from each group during the MWM probe test. *<i>p</i><0.05, **<i>p</i><0.01, compared to the MCAO group. †<i>p</i><0.05, ††<i>p</i><0.01, †††<i>p</i><0.001, compared to the AZT group.</p

Hippocampal HIF-1α, c-Fos, and pMAPK expression increased gradually with increasing numbers of post-ischemia IH interventions.

<p>(A) Experimental design. Ischemic rats were exposed to differing numbers (1, 3, 5, or 7) of IH interventions or sham IH sessions. (B) Immunoblotting was used to detect hippocampal HIF-1α, pMAPK, MAPK, and c-Fos expression. (C–E) Quantification of immunoblotting results. *<i>p</i><0.05, **<i>p</i><0.01, compared to the MCAOIH ×7 group. †<i>p<</i>0.05, ††<i>p<</i>0.01, compared to the MCAO group.</p

Post-ischemia IH intervention induced hippocampal neurogenesis.

<p>(A) Schematic depicting hippocampal subregions of interest. (B) BrdU⁺ cells in each hippocampal subregion (bar, 100 µm). The lower right image is a 40× magnification of the region boxed in white (bar, 50 µm). BrdU⁺ cells are indicated by arrows. BrdU⁺ cells were expressed primarily in the DG. (C, top) BrdU staining in the AZT group as compared to the MCAOIH group. (C, bottom) Quantification of BrdU staining. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001, compared to the AZT group. ††<i>p</i><0.01, †††<i>p</i><0.001, compared to the MCAOIH group. #<i>p</i><0.05, ###<i>p</i><0.001, compared to the Sham group.</p

Post-ischemia IH intervention enhanced the activity of newborn cells, as indicated by c-Fos expression.

<p>Newborn cell activity correlated significantly with spatial memory improvement. (A) BrdU (red; upper left) and c-Fos (green; upper right) staining in the DG (bar, 100 µm). The lower right image is a 40× magnification of the region boxed in white (lower left). BrdU⁻/c-Fos⁺ cells are indicated by stars. BrdU⁺/c-Fos⁺ cells are indicated by arrows. BrdU⁺/c-Fos⁻ cells are indicated by arrowheads. (B) Quantification of BrdU⁺/c-Fos⁺ double-labeling. (C) Correlation of the number of BrdU⁺/c-Fos⁺ double-labeled cells with memory improvement ratios. ***<i>p<</i>0.001 compared to the AZT group. †††<i>p<</i>0.001 compared to the MCAO group.</p

Post-ischemia IH intervention enhanced hippocampal cellular activity as indicated by c-Fos expression.

<p>(A) c-Fos staining in each hippocampal subregion (bar, 100 µm). The lower right image is a 40× magnification of the region boxed in white (bar, 50 µm). c-Fos⁺ cells are indicated by arrows. (B, top) c-Fos staining in the AZT group as compared to the MCAOIH group. (B, bottom) Quantification of c-Fos staining. **<i>p<</i>0.01, ***<i>p<</i>0.001, compared to the AZT group. ††<i>p<</i>0.01, †††<i>p<</i>0.001, compared to the MCAOIH group. ###<i>p<</i>0.001 compared to the NorIH group.</p

The relative expression of apoptotic cells in the peri-infarct area (primary motor cortex, M1) (n = 8 for each group).

<p><b>A:</b> Expression of TUNEL positive and Hoechst cells among groups. <b>B:</b> The peri-infarct area for measurement. <b>C:</b> Quantification of the percentage of TUNEL positive cells to Hoechst cells. *, **, <i>P</i><0.05, <i>P</i><0.01 vs. S group; ##, <i>P</i><0.01 vs. C group; ++, <i>P</i><0.01 vs. IGF group. S: Sham control; C: MCAO control; IGF: MCAO with IGF-I treatment; IGF+I: MCAO with AG1024 and IGF-I treatment.</p

The IGF-I concentrations in the tissue samples and plasma (n = 8 for each group).

<p><b>A:</b> The IGF-I concentrations of the left sciatic nerve, total lumbar spinal cord and right motor cortex. <b>B:</b> The IGF-I concentrations of the left hind-limb muscles. <b>C:</b> The IGF-I concentrations of the plasma. *, **, <i>P</i><0.05, <i>P</i><0.01 vs. S group; ##, <i>P</i><0.01 vs. C group; ++, <i>P</i><0.01 vs. IGF group. S: Sham control; C: MCAO control; IGF: MCAO with IGF-I treatment; IGF+I: MCAO with AG1024 and IGF-I treatment.</p

The motor performances in the parallel bar crossing test (n = 8 for each group).

<p>**, <i>P</i><0.01 vs. S group; ##, <i>P</i><0.01 vs. C group. S: Sham control; C: MCAO control; IGF: MCAO with IGF-I treatment; IGF+I: MCAO with AG1024 and IGF-I treatment.</p

Effects of evodiamine(EVO)on the proliferation of MCF-7 and MDA-MB-231.

<p>The incubation period was from 1 to 4 days. Proliferation index was measured by MTT assay. Each value presents mean plus or minus SEM. * <i>p</i><0.05, ** <i>p</i><0.01 as compared to corresponding vehicle group.</p