Edaravone-mediated oxygen radical scavenging promotes blood-brain barrier repair in rats with stroke

Objective To investigate the effect of edaravone on the blood-brain barrier in rats with ischemic stroke and related mechanism. Methods A model of cerebral ischemia-reperfusion in Wistar rats was established through the Longa method. The nervous function of these rats were established on the next day. Then, the rats were randomly divided into the following groups (n=12): two cerebral ischemia/reperfusion groups (group I/R-24 h and group I/R-7 d), a low-dose edaravone group (group Eda-L) and a high-dose edaravone group (group Eda-H). The rats in group I/R-24 h were sacrificed after the behavioral test. Rats in other groups were injected with edaravone or normal saline via the tail vein once daily for consecutive seven days, and then the neurological function scores were re-evaluated. The rats were sacrificed and their brain tissues were collected. The cerebral infarction volume was detected by 2, 3, 5-triphenyltetrazolium chloride (TTC) method. The water content was examined by dry and wet weight method. The integrity of the blood-brain barrier was detected by Evans blue (EB) trace method. The levels of oxidative factors were measured by ELISA kits. The levels of MMP-9, Claudin-5, and Occludin were detected by Western blot. Results I/R caused increases in neurological function scores in rats, with infarction in the brain. Compared with group Sham, group I/R showed remarkable increases in EB content in the brain tissue and water content. However, compared with group I/R, group Eda-H presented significantly decreased neurological scores and infarct area, with reduced EB penetrating rate and the water content restored to the baseline. In addition, compared with I/R group, group Eda-H showed reduced contents of oxidative stress factors and increased levels of MMP-9, Claudin-5 and Occludin. Conclusions Edaravone can enhance the scavenging of oxygen free radicals, dow-regulate the level of MMP-9, promote the repair of the blood-brain barrier, and improve the neurological function and cerebral edema in rats.