Effects of edaravone on glial fibrillary acidic protein and interleukin-lβ expression and neuronal apoptosis in juvenile rat hippocampus after status convulsion / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of edaravone on glial fibrillary acidic protein (GFAP) and interleukin-1β (IL-lβ) expression and neuronal apoptosis in the juvenile rat hippocampus after status convulsion (SC).</p><p><b>METHODS</b>One hundred and ninety-five juvenile male Sprague-Dawley (SD) rats were randomly divided into 3 groups: normal saline control and SC with and without edaravone treatment. Each of the 3 groups was further subdivided into subgroups sacrificed at 4, 12, 24, 48 and 72 hrs after SC (n=15). The SC model was prepared using lithium-pilocarpine. The expression of GFAP and IL-lβ protein was detected with immunohistochemistry methods. The neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). The hippocampal GFAP mRNA expression was detected by RT-PCR.</p><p><b>RESULTS</b>The value of IOD of GFAP and IL-lβ positive cells measured by immunohistochemistry in the untreated SC group increased compared with the control group. Expression of GFAP and IL-lβ protein was significantly reduced in the edaravone treated SC group compared with the untreated SC group. RT-PCR showed the expression trend of GFAP mRNA was similar to that of protein. The TUNEL positive cells in the hippocampus CA1 in the untreated SC group increased significantly 12 hrs after SC and reached a peak at 48 hrs compared with the control group. The intervention with edaravone decreased significantly TUNEL positive cells between 12-48 hrs after SC, but the number of TUNEL positive cells in the intervention group remained significantly greater than in the control group.</p><p><b>CONCLUSIONS</b>The expression of GFAP and IL-lβ in the hippocampus increases after SC in rats. Edaravone may decrease the expression of GFAP and IL-1β and reduce the number of neuronal apoptosis. These results suggest that edaravone may have protective effects against brain damage caused by SC.</p>

Effects of edaravone on IRE1 mRNA expression and neuronal apoptosis in the hippocampus of rats with status convulsivus / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the expression of the key marker of endoplasmic reticulum stress (ERS) IRE1 mRNA and neuronal apoptosis in the rat hippocampus after status convulsivus (SC), and the intervention effects of edaravone, a novel free radical scavenger.</p><p><b>METHODS</b>Sprague-Dawley (SD) rats aged 19-21 days were randomly assigned to three groups: normal control, SC and edaravone-treated SC. SC was induced in the later two groups. The two groups were subdivided into 5 groups sacrificed at 4, 12, 24, 48, and 72 hrs after SC induction. IRE1 mRNA expression in the hippocampus was detected by RT-PCR. Neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). The ultramicrostructural changes of neuron were observed by electron microscopy.</p><p><b>RESULTS</b>IRE1 mRNA expression was obviously up-regulated 4 and 12 hrs after SC compared with the normal control group (P<0.01). IRE1 mRNA expression in the edaravone-treated SC group was notably higher than the untreated SC group 4, 12 and 24 hrs after SC and the normal control group (P<0.01). TUNEL positive cells in the hippocampus in the untreated SC group were significantly more than those in the normal control group (P<0.01). The number of TUNEL positive cells increased with the prolonged convulsion time. TUNEL positive cells in the edaravone-treated SC group were significantly reduced compared with those in the untreated SC group 12, 24, 48 and 72 hrs after SC (P<0.05 or P<0.01), but remained higher than the normal control group (P<0.05 or P<0.01). The peri-nucleus cell organ injuries were observed 4 hrs after SC and karyopycnosis and cytoplasm condensation were observed 12 hrs after SC in the SC and the edaravone-treated SC groups. The edaravone-treated SC group demonstrated less severe apoptosis than the untreated SC group.</p><p><b>CONCLUSIONS</b>Edaravone may have neuroprotections against SC by an up-regulation of IRE1 expression. It might serve as an effective agent for reducing ERS in vivo.</p>

Effects of edaravone on the expression of interleukin-1beta, nuclear factor-kappaB and neuron apoptosis in juvenile rat hippocampus after status convulsion / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of edaravone on expression of interleukin-1beta (IL-1beta), nuclear factor-kappaB (NF-kappaB) and neuron apoptosis in the juvenile rat hippocampus after status convulsion (SC).</p><p><b>METHODS</b>One hundred and ninety-five juvenile male Sprague-Dawley (SD) rats were randomly divided into normal saline (NS) control group, status convulsive group and edaravone treatment group. Each group was further divided into five subgroups for different time points. The rats in status convulsive group were kindled into epilepsy by lithium-pilocarpine chemical method. Expressions of IL-1beta and NF-kappaB proteins were detected with immunohistochemistry methods. Expression of NF-kappaB mRNA was detected with reverse transcription-polymerase chain reaction (RT-PCR). The neuron apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL).</p><p><b>RESULTS</b>(1) Measured by immunohistochemistry the value of IOD of IL-1beta (30.83 +/- 3.81, 41.00 +/- 5.61, 36.32 +/- 6.78 and 28.48 +/- 4.61, respectively, 12-72 h points) and NF-kappaB (67.60 +/- 5.81, 74.61 +/- 7.94, 82.43 +/- 10.67, 70.70 +/- 5.85 and 68.22 +/- 9.67, respectively, 4-72 h points) positive cells in the SC group increased,there was significant difference compared with NS group (IL-1beta: 11.74 +/- 2.32, 12.93 +/- 2.49, 13.02 +/- 2.83 and 12.98 +/- 5.29, respectively, 12-72 h points. NF-kappaB: 48.67 +/- 16.14, 44.62 +/- 7.82, 53.16 +/- 114.45, 54.27 +/- 5.25 and 55.56 +/- 7.56, respectively, 4-72 h points) (P < 0.01, or P < 0.05). By ED intervention in IL-1beta (22.01 +/- 4.45, 28.28 +/- 4.50 and 26.00 +/- 5.34, respectively, 12-48 h points) and NF-kappaB (58.56 +/- 6.37, 59. 86 +/- 6.73, 70.00 +/- 10.09, 64.78 +/- 7.56 and 64.45 +/- 6.51, respectively, 4-72 h points) positive cells value of the IOD decreased as compared with SC group (P < 0.01, or P < 0.05). (2) Measured by RT-PCR, the expression of NF-KB mRNA and protein trend was similar. (3)The TUNEL positive cells in hippocampus, CA1 of SC group (11.41 +/- 2.37) were more than that of NS group 12 h after the SC (P < 0.01), reached its highest level at48 h (28.78 +/- 5.11), after the intervention with edaravone (8.98 +/- 2.22, 13.09 +/- 2.54 and 20. 57 +/- 4.89, respectively, 12-48 h points) ,TUNEL positive cells showed a significant drop in SC group at 12-48 h time points (P < 0.01, or P < 0.05), but still significantly higher than that of the NS group (6.22 +/- 1.50, 6.57 +/- 1.61 and 6.72 +/- 1.14, respectively) (P < 0.01, or P < 0.05), at the 4 h time point(NS group 6.29 +/- 1.49, SC group 6.61 +/- 1.71, ED group 5.75 +/- 1.41) among the three groups, no significant difference in TUNEL positive cells was found (P = 0.759).</p><p><b>CONCLUSIONS</b>Edaravone inhibited expression of IL-1beta and NF-kappaB in pilocarpine-induced seizures in rat hippocampus, reduced the number of neuronal apoptosis. These results suggest that edaravone may have protective effect against the damage caused by status convulsion.</p>