Edaravone is a novel free radical scavenger that is clinically employed in 
patients with acute cerebral infarction, but has not previously been used to 
treat traumatic brain injury (TBI). In this study, we investigated the effect of 
edaravone administration on rat TBI. In particular, we used immunohistochemistry 
to monitor neural stem cell (NSC) proliferation around the area damaged by TBI. 
Two separate groups of rats were administered saline or edaravone (3 mg/kg) 
after TBI and then killed chronologically. We also used ex vivo techniques to 
isolate NSCs from the damaged region and observed nestin-positive cells at 1, 3, 
and 7 days following TBI in both saline- and edaravone-treated groups. At 3 days 
following TBI in both groups, there were many large cells that morphologically 
resembled astrocytes. At 1 and 7 days following TBI in the saline group, there 
were a few small nestin-positive cells. However, in the edaravone group, there 
were many large nestin-positive cells at 7 days following TBI. At 3 and 7 days 
following TBI, the number of nestin-positive cells in the edaravone group 
increased significantly compared with the saline group. There were many 
single-stranded DNA-, 8-hydroxy-2'-deoxyguanosine-, and 
4-hydroxy-2-nonenal-positive cells in the saline group following TBI, but only a 
few such cells in the edaravone group following TBI. Furthermore, almost all 
ssDNA-positive cells in the saline group co-localized with Hu, nestin, and glial 
fibrillary acidic protein (GFAP) staining, but not in the edaravone group. In 
the ex vivo study, spheres could only be isolated from injured brain tissue in 
the saline group at 3 days following TBI. However, in the edaravone group, 
spheres could be isolated from injured brain tissue at both 3 and 7 days 
following TBI. The number of spheres isolated from injured brain tissue in the 
edaravone group showed a significant increase compared with the saline group. 
The spheres isolated from both saline and edaravone groups were immunopositive 
for nestin, but not Tuj1 or vimentin. Moreover, the spheres differentiated into 
Tuj1-, GFAP-, and O4-positive cells after 4 days in culture without bFGF. This 
result indicated that the spheres were neurospheres composed of NSCs that could 
differentiate into neurons and glia. Edaravone administration inhibited 
production of free radicals known to induce neuronal degeneration and cell death 
after brain injury, and protected nestin-positive cells, including NSCs, with 
the potential to differentiate into neurons and glia around the area damaged by 
TBI.