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![Selective exchange protein directly
activated by cAMP 2 inhibitor (ESI-05) administration decreases
acute permanent cerebral infarcts in rats. (A) Control group. (B)
ESI-05 group. Brains were extracted 24 h after ischemia and
subjected to 2,3,5-triphenyltetrazolium chloride staining to
visualize live mitochondria during the sacrifice process. Necrotic
tissue was distinguished in all images by the lack of red staining,
signifying the presence of non-metabolically active mitochondria at
the time of sacrifice. (C-E) Quantification of lesion size in the
middle cerebral artery occlusion model. Effects of ESI-05 treatment
on (C) infarct volume (% indirect) and (D) brain water content in
the left cerebral hemisphere at 24 h after cerebral infarction. (E)
Effects of ESI-05 treatment on the neurological score 24 h after
ischemia. Sham, no data; control group, n=11; and ESI-05 group,
n=11. Data are presented as the mean ± standard deviation of the
mean for infarct volume and brain water content. Data are presented
as the median and interquartile range for neurological score.
*P<0.05, ***P<0.001. ESI-05,
1,3,5-trimethyl-2-[(4-methylphenyl)sulfonyl]-benzene.](/article_images/etm/30/3/etm-30-03-12922-g00.jpg)
![Epac2 expression in the peri-infarct
area. (A) Increased numbers of Epac2-positive cells were observed
in the peri-infarct area in the control group. (B) However, fewer
Epac2-positive cells were found in the peri-infarct area in the
ESI-05 group. Sham group, no data; control group, n=2; and ESI-05
group, n=2. Scale bar, 50 µm (magnification, x200). (C) Epac2
expression in the peri-infarct region was assessed using western
blot analysis. Sham group, n=8; control group, n=8; and ESI-05
group, n=6. The ESI-05 group exhibited notably reduced Epac2
expression compared with the control group [F (2, 19)=18.9;
P<0.001]. *P<0.05, ***P<0.001.
Epac2, exchange protein directly activated by cyclic adenosine
monophosphate 2; ESI-05,
1,3,5-trimethyl-2-[(4-methylphenyl)sulfonyl]-benzene.](/article_images/etm/30/3/etm-30-03-12922-g01.jpg)
![p38 MAPK signaling pathway in the
peri-infarct area. (A) Increased numbers of cleaved caspase
3-positive cells were observed in the peri-infarct area in the
control group. (B) Fewer cleaved caspase 3-positive cells were
found in the peri-infarct area in the ESI-05 group. Sham group, no
data; control group, n=2; and ESI-05 group, n=2. Scale bar, 20 µm
(magnification, x200). (C) Western blot images were derived from
separate regions of the same membrane, as indicated by the white
lines. (D) Cleaved caspase 3 levels in the peri-infarct region were
assessed using western blot analysis. Sham group, n=8; control
group, n=8; and ESI-05 group, n=6. The ESI-05 group exhibited
markedly reduced levels of cleaved caspase 3 compared with the
control group [F (2, 19)=31.3; P<0.001]. (E) Phospho-p38 MAPK
levels in the peri-infarct area were semi-quantified using western
blotting. Sham group, n=8; control group, n=8; and ESI-05 group,
n=6. The levels of phospho-p38 MAPK expression in the ESI-05 group
exhibited a statistically significant decrease compared with those
in the control group [F (2, 19)=35.7; P<0.001]. (F) Activation
levels of caspase 3 analyzed in terms of the ratio of cleaved
caspase 3 to total caspase 3. (G) Phosphorylation levels of p38
analyzed in terms of the ratio of P-p38 to total p38.
*P<0.05, **P<0.01,
***P<0.001. C-, cleaved; cas3, caspase 3; Epac2,
exchange protein directly activated by cyclic adenosine
monophosphate 2; ESI-05,
1,3,5-trimethyl-2-[(4-methylphenyl)sulfonyl]-benzene; P-,
phosphorylated.](/article_images/etm/30/3/etm-30-03-12922-g02.jpg)
![Representative images of TUNEL and
FJC staining of brain tissue from the control and ESI-05-treated
offspring at 24 h. Sham group, no data; control group, n=2; and
ESI-05 group, n=2. TUNEL- and FJC-positive cells were decreased in
the brains of ESI-05-treated offspring at 24 h. Scale bar, 50 µm
(magnification, x200). ESI-05,
1,3,5-trimethyl-2-[(4-methylphenyl)sulfonyl]-benzene; FJC, fluoro
Jade C.](/article_images/etm/30/3/etm-30-03-12922-g03.jpg)
