Department of Neurosurgery, Affiliated Hospital of Northern China Coal Medical College, Tangshan 063000, China.
World J Emerg Med. 2011;2(3):222-7. doi: 10.5847/wjem.j.1920-8642.2011.03.012.
Edaravone can alleviate brain injury and improve neurological functions and symptoms. This study aimed to investigate the effect of edaravone on the p38Mitogen-activated protein kinases/Caspase-3 (p38MAPK /Caspase-3) pathway after diffuse brain injury (DBI) in rats.
DBI models were established according to the description of Marmarou's method. A total of 250 rats were divided (random number) into four groups: control group (CG, n=45), model group (MG, n=77), low-dose edaravone group (n=67, dosage 5 mg/kg) and high-dose edaravone group (n=61, dosage 10 mg/kg). After 1, 6, 24, 48, and 72 hours after injury, brain tissues were collected. The changes of neuron morphous in the hippocampal region were observed through Nissl staining. The expression levels of phosphorylated p38MAPK and caspase-3 were detected by immunohistochemistry and Western blotting respectively. Learning and memory function were tested with Morris water maze from the 3rd to 7th day after injury.
Some neurons had histopathologic changes of necrosis and apoptosis in the model group compared with the control group. The phosphorylated p38MAPK expressions increased at 1, 6, 4, and 48 hours (P<0.05), but no significant difference was observed at 72 hours (0.54±0.19 vs. 0.40±0.14, P>0.05). Caspase-3 expressions increased at 6, 24, 48, and 72 hours respectively (P<0.05), but there was no significant difference at 1 hour (0.59±0.29 vs. 0.40±0.17, P>0.05). From the 3rd to 6th day during the Morris water maze test, the latency to find the platform was significantly prolonged (P<0.05) and times of rats crossing the platform was decreased on the 7th day (2.28±1.18 vs. 8.20±1.52, P<0.05). The phosphorylated p38MAPK expressions decreased at 6, 24 and 48 hours respectively in the low dose edaravone group compared with the model group (P<0.05), whereas no significant difference was seen at 1 hour (1.66±0.80 vs. 1.85±0.86, P>0.05). Caspase-3 expression decreased at 6, 24, 48, and 72 hours (P<0.05). The latency to find the platform was significantly shortened (P<0.05), and times of rats crossing the platform increased (4.17±1.15 vs. 2.28±1.18, P<0.05). The above mentioned parameters changed more significantly in the high-dose edaravone group than in the low-dose edaravone group.
Edaravone can alleviate brain tissue damage after DBI, inhibit p38MAP signal activation after early injury, reduce the expression of caspase-3, and promote the recovery of neurological function in the late period.
依达拉奉可减轻脑损伤，改善神经功能和症状。本研究旨在探讨依达拉奉对大鼠弥漫性脑损伤（DBI）后 p38 丝裂原活化蛋白激酶/Caspase-3（p38MAPK/Caspase-3）通路的影响。
根据 Marmarou 方法的描述建立 DBI 模型。共 250 只大鼠随机分为四组：对照组（CG，n=45）、模型组（MG，n=77）、低剂量依达拉奉组（n=67，剂量 5mg/kg）和高剂量依达拉奉组（n=61，剂量 10mg/kg）。损伤后 1、6、24、48 和 72 小时取脑组织。通过尼氏染色观察海马区神经元形态变化。分别通过免疫组织化学和 Western blot 检测磷酸化 p38MAPK 和 caspase-3 的表达水平。伤后第 3-7 天用 Morris 水迷宫测试学习和记忆功能。
与对照组相比，模型组部分神经元有坏死和凋亡的组织病理学改变。磷酸化 p38MAPK 表达在 1、6、4 和 48 小时增加（P<0.05），但在 72 小时无显著差异（0.54±0.19 vs. 0.40±0.14，P>0.05）。Caspase-3 表达在 6、24、48 和 72 小时分别增加（P<0.05），但在 1 小时无显著差异（0.59±0.29 vs. 0.40±0.17，P>0.05）。在 Morris 水迷宫测试的第 3-6 天，找到平台的潜伏期明显延长（P<0.05），第 7 天穿越平台的次数减少（2.28±1.18 vs. 8.20±1.52，P<0.05）。与模型组相比，低剂量依达拉奉组在 6、24 和 48 小时磷酸化 p38MAPK 表达降低（P<0.05），而在 1 小时无显著差异（1.66±0.80 vs. 1.85±0.86，P>0.05）。Caspase-3 表达在 6、24、48 和 72 小时降低（P<0.05）。找到平台的潜伏期明显缩短（P<0.05），穿越平台的次数增加（4.17±1.15 vs. 2.28±1.18，P<0.05）。高剂量依达拉奉组上述参数的变化比低剂量依达拉奉组更明显。
依达拉奉可减轻 DBI 后脑组织损伤，抑制早期损伤后 p38MAP 信号的激活，降低 caspase-3 的表达，促进后期神经功能的恢复。
