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).
CONCLUSION: 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.