Cross-correlation histograms show coincident firing of a sample pair of neurons from one SE rat between the baseline period and early preictal period.

<p>Black line indicates the raw correlation smoothed with a 7 ms boxcar window (CCH_raw). The jitter-predicted correlation (Jitter₅₀, blue) indicates the correlation driven by common input, as determined by jitter shuffling of the spike train with a 50 ms window. The cross-correlogram (‘CCG’, or COIN₅₀, red) corresponds to pair-specific coincident activity, defined as the difference between raw coincidences and jitter coincidences.</p

Recording and analysis profiles of neuronal ensembles.

<p><b>A</b>. Histological locations (asterisks) of recording electrode tips in the hippocampus. Scale bar indicates 500 μm. <b>B</b>. Waveforms of hippocampal spikes (yellow) and noise signals (whitish-gray) separated by morphology (calibration: 0.2 ms, 100 μV). <b>C</b>. Clusters of single units and noise signals separated according to the first two principal components (PC1 on x-axis; PC2 on y-axis). <b>D</b>. Autocorrelogram of a single unit with an absolute refractory period of a minimum of 2 ms.</p

Changes in the firing rates of hippocampal units in pilocarpine-treated rats.

<p><b>A</b>. Relative discharge rates 30 min before and after pilocarpine treatment in SE (red) and nonSE (blue) rats. <b>B</b>. Rate-by-rate comparison of firing rate change before [-10∶0 minute] and after [5∶15 minute] pilocarpine injection (see gray zones in panel A) of individual neurons from SE (red dots) and nonSE (blue dots) rats. Filled circles indicate significant difference of firing rate after pilocarpine injection. Open circles indicate no change in firing rate.</p

Changes in functional connectivity across all neuronal pairs from cross-correlation analysis.

<p>Upper panel shows the raw correlation (CCH_raw), correlation driven by common input (Jitter₅₀), and correlation of neuronal pairs (COIN₅₀) based on peak values at baseline and early preictal periods. Lower panel shows log ratios of the coincident peak of early preictal period to that of baseline period. The vertical scatter plots integrate the distributions of all ratio results in CCH_raw, Jitter₅₀, and COIN₅₀. Each data point represents a result from one neuronal pair. The mean peak ratio is indicated by black horizontal line, and the median peak ratio is shown in green. The correlation value of neuronal pairs was significantly larger in nonSE rats than SE rats.</p

Local field potentials in 10-sec time windows of representative SE and nonSE rats at baseline period (upper panel) and at 5 min (middle panel) and 85 min (lower panel) after pilocarpine treatment.

<p>Local field potentials in 10-sec time windows of representative SE and nonSE rats at baseline period (upper panel) and at 5 min (middle panel) and 85 min (lower panel) after pilocarpine treatment.</p

Outline of the experimental procedure.

<p><b>A</b>. Experimental steps for induction of status epilepticus (SE). <b>B</b>. Temporal profiles of SE in 9 rats after injection of pilocarpine. No SE was identified in 12 rats. The black bar indicates the occurrence of SE. The early post-pilocarpine period was defined as the time period of 5–15 min after injection of pilocarpine, as delimited between the two vertical dashed lines.</p

Mean onset time (± SEM) of status epilepticus (SE) relative to behavioral and local field potential (LFP) patterns after i.p. pilocarpine injection in nonSE and SE groups.

<p>Mean onset time (± SEM) of status epilepticus (SE) relative to behavioral and local field potential (LFP) patterns after i.p. pilocarpine injection in nonSE and SE groups.</p

BMX inhibited tumor-induced neovascularization and suppressed <i>in vivo</i> tumor growth in nude mice.

<p>(A) HCT 116 colorectal cancer cells were mixed with Matrigel and then injected subcutaneously into the right flank of nude mice. After implantation, animals were treated intraperitoneally with vehicle or BMX 20 mg/kg/day for 10 days. Matrigel plugs removed from the mice administered intraperitoneally with vehicle or BMX were shown. (B) The blood vessels in the Matrigel plug were stained with anti-CD31 antibody as described in the “<i>Materials and Methods</i>” section. Images of immunohistochemical staining representative of three independent Matrigel plug with similar results are shown. (C) Hemoglobin levels in the Matrigel plug shown in (A) were quantified. Each column represents the mean ± S.E.M. of six plugs in each group (^*p<0.05 as compared with the vehicle-treated control group, n = 5). (C) Nude mice bearing xenografts of HCT116 colorectal cancer cells were treated intraperitoneally with BMX 20 mg/kg/day for 22 days. The control group received vehicle only. Tumor volumes were calculated as described in the <i>Materials and Methods</i> section. Values represents the mean ± S.E.M. (^*p<0.05 as compared with the vehicle-treated control group, n = 5). (D) After 22 days of treatment as in (C), mice were sacrificed and tumors were dissected and weighted. Each column represents the mean ± S.E.M. (^*p<0.05 as compared with the vehicle-treated control group, n = 5). (E) The body weights of the nude mice were examined within 22 days treatment of vehicle or BMX. Values represent the mean ± S.E.M.</p

BMX inhibited VEGF-induced migration, tube formation and microvessel sprouting.

<p>(A) HUVECs were starved in 2% FBS containing medium without ECGS for 16 h. Cell monolayer were then scratched and treated with vehicle or indicated concentrations of BMX in the presence of VEGF for another 16 h. The number of migrated cells was then determined. Each column represents the mean ± S.E.M. of four independent experiments. *<i>p</i><0.05, compared with the group treated with VEGF alone. (B) After starvation as described in (A), Cells were then seeded in the top chamber in the absence or presence of BMX (5 µM) using VEGF as chemo-attractant. After 16 h, invaded cells through the gelatin-coated membrane were stained and quantified. Each column represents the mean ± S.E.M. of four independent experiments. *<i>p</i><0.05, compared with the group treated with VEGF alone. (C) HUVECs were seeded on Matrigel in the presence of VEGF (20 ng/ml) with or without BMX at indicated concentrations. Cells were then photographed under phase-contrast microscopy after 16 h. Bar graphs show compiled data of average sprout arch numbers (n = 4). *<i>p</i><0.05, compared with the group treated with VEGF alone. (D) Rat aortic rings were placed in Matrigel and treated with VEGF (20 ng/ml) in the presence or absence of BMX (5 µM). The effect of BMX on formation of vessel sprout from various aorta samples was examined on day 8. Bar graphs show compiled data of average microvessels area (n = 4). *<i>p</i><0.05, compared with the group treated with VEGF alone.</p

BMX affected the protein levels of p21^cip/Waf1, cyclinD1, CDK4 and survivin in HUVECs.

<p>Cells were treated with indicated concentrations of BMX for 24^cip/Waf1, cyclinD1, CDK4 and survivin were then determined by immunoblotting. Figures shown in (A) are representative of four independent experiments with similar results. The compiled results of p21^cip/Waf1 (B), cyclinD1 (C), CDK4 (D), and survivin (E) levels are shown. Each column represents the mean ± S.E.M. of four independent experiments. *<i>p</i><0.05, compared with the control group</p