title: Protective effects of edaravone on diffuse brain injury in rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Northern China Coal Medical College, Tangshan 063000, China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Northern China Coal Medical College, Tangshan 063000, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Northern China Coal Medical College, Tangshan 063000, China.
authors.forename: Ya-Ning
authors.initials: YN
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Northern China Coal Medical College, Tangshan 063000, China.
authors.forename: Chang-Xiang
authors.initials: CX
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Northern China Coal Medical College, Tangshan 063000, China.
authors.forename: Shu-Xing
authors.initials: SX
authors.lastname: Li
keywords: Caspase-3; Diffuse brain injury; Edaravone; Learning-memory; Mitogen-activated protein kinases