title: [Effect of edaravone on extracellular signal-regulated kinase 1/2 pathway following severe traumatic brain injury in rats].
abstract: OBJECTIVE
  To study the protective effect of edaravone on severe traumatic brain injury (TBI) and its potential mechanism.
  
  
  METHODS
  Two hundred and seventy-three male Sprague-Dawley (SD) rats were divided randomly into four groups: control group (n=45), model group (n=88), low-dose edaravone treatment group (n=72), high-dose edaravone treatment group (n=68). TBI rat model was reproduced by weight-dropping injury. One, 6, 24, 48 and 72 hours after injury, changes in brain tissue were observed with light and electron microscopy. The expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was determined by Western blotting. The rate of neuron apoptosis was observed with immunohistochemistry and terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. Learning and memory function assessments were performed with Morris water maze from 7th day to 10th day after injury.
  
  
  RESULTS
  Compared with control group, a part of neurons in hippocampus displayed histopathologic changes denoting necrosis 6, 24, 48 and 72 hours after injury. The p-ERK1/2 expression level (pg/unit) increased 1, 6, 24, 48 hours after injury (2.05 + or - 0.40, 4.40 + or - 0.96, 6.70 + or - 0.87, 3.67 + or - 0.28 vs. 0.40 + or - 0.04, 0.41 + or - 0.05, 0.43 + or - 0.06, 0.40 + or - 0.03), and the number of apoptotic cells increased 6, 24, 48, 72 hours after injury (9.60 + or - 2.69, 12.68 + or - 2.99, 16.94 + or - 3.92, 25.82 + or - 4.61 vs. 2.42 + or - 0.38, 2.58 + or - 0.57, 2.74 + or - 0.56, 2.61 + or - 0.58); latent period to find the safety platform (s) was significantly prolonged (119.8 + or - 25.0, 105.6 + or - 24.5, 98.5 + or - 21.8, 92.0 + or - 19.5 vs. 49.5 + or - 7.5, 32.7 + or - 6.3, 25.8 + or - 6.5, 24.8 + or - 5.5, all P<0.05). After treatment with edaravone, the degree of morphological injury, p-ERK1/2 level and number of apoptotic neurons decreased, latent period to find the safety platform was significantly shortened (in low-dose edaravone treatment group, p-ERK1/2 expression level at 6, 24, 48 hours was 2.46 + or - 0.22, 4.00 + or - 0.84, 2.38 + or - 0.32, and in high-dose edaravone treatment group was 1.67 + or - 0.15, 1.86 + or - 0.38, 1.27 + or - 0.28; in low-dose edaravone treatment group, the apoptotic cells at 6, 24, 48, 72 hours was 5.20 + or - 1.23, 7.10 + or - 1.72, 9.54 + or - 1.36, 14.12 + or - 3.19, and in high-dose edaravone treatment group was 3.40 + or - 0.49 , 4.39 + or - 0.73, 5.02 + or - 1.12, 8.78 + or - 2.16; in low-dose edaravone treatment group, latent period to find the safety platform at 7-10 days was 94.8 + or - 22.8, 65.2 + or - 19.0, 62.0 + or - 16.7, 59.5 + or - 15.6, and in high-dose edaravone treatment group it was 81.5 + or - 20.7, 55.4 + or - 18.5, 40.0 + or - 12.3, 32.2 + or - 11.0, all P<0.05). High-dose edaravone showed a better effect (all P<0.05).
  
  
  CONCLUSIONS
  Edaravone gives good therapeutic effect on severe TBI, and the molecular mechanism is related to attenuation of ERK1/2 pathway and neuronal apoptosis following severe brain trauma.
authors.affiliation: Basic Medicine Department of North China Coal Medical College, Tangshan 063000, Hebei, China.
authors.forename: Ya-ning
authors.initials: YN
authors.lastname: Zhao
authors.forename: Xia
authors.initials: X
authors.lastname: Guo
authors.forename: Jun-ling
authors.initials: JL
authors.lastname: Gao
authors.forename: Hai-hong
authors.initials: HH
authors.lastname: Chen
authors.forename: Yan-xia
authors.initials: YX
authors.lastname: Tian
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Cui
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D000077553:Edaravone; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077553:Edaravone; D000983:Antipyrine