Edaravone is clinically used for treatment of patients with acute
cerebral infarction. However, the effect of double application of
edaravone on neurogenesis in the hippocampus following
ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of
edaravone had any effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of hippocampus in a rat model of transient global
cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups:
sham-operated (n = 15), control (n = 15), and
edaravone-treated (n = 15) groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis.
Terminal deoxynucleotidyl transferase-mediated dUTP-
biotin nick-end labeling was used to detect cell apoptosis.
Reactive oxygen species (ROS) were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro.
Hypoxia-inducible factor-1α (HIF-1α) and cleaved
caspase-3 proteins were quantified by western blot analysis. Treatment with
edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p < .05). Treatment with
edaravone also decreased apoptosis of NSPCs (p < .01). Furthermore, treatment with
edaravone significantly decreased ROS generation and inhibited HIF-1α and cleaved
caspase-3 protein expressions. These findings indicate that pre- and posttreatment with
edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting
protein expressions of HIF-1α and cleaved
caspase-3 after
cerebral ischemia.