Protective effects of AER-271 in acute-phase radiation-induced brain injury in rats: reduction of brain edema, inflammation, apoptosis and maintenance of blood-brain barrier integrity.

OBJECTIVE: The expression changes of aquaporin-4 (AQP4) in radiation-induced brain jinjury (RIBI) and whether it is involved in the pathologic development of RIBI are currently unknown. In this study, we constructed a RIBI model by whole-brain radiation of Sprague-Dawley (SD) rats and tried to reveal the role of AQP4 in RIBI. The specific inhibitor AER-271 was used to inhibit the expression of AQP4 in RIBI to explore its neuro-protective effect. METHODS: SD rats were randomly divided into Sham group and IR group. The trend and role of AQP4 in RIBI were explored by H&E staining, Western blot, brain tissue water content measurement, Evans blue (EB) osmolality assay, and immunofluorescence staining. Then SD rats were randomly divided into Sham group, AER-271 group, IR group and IR+AER-271 group to investigate the neuroprotective effects of AER-271 by H&E staining, Western blot, brain tissue water content measurement, EB osmolality assay, immunofluorescence staining, qRT-PCR and Elisa. RESULTS: Radiation promoted the expression of AQP4 in rat brain tissue, leading to its "depolarized" distribution. The expression level of AQP4 correlated with the severity of cerebral edema. Treatment with AER-271 reduced cerebral edema, attenuated inflammation and apoptosis, and maintained the integrity of the blood-brain barrier (BBB) in RIBI rats. CONCLUSION: AQP4 is involved in regulating the subsequent inflammatory response, BBB injury and apoptosis by mediating the development of cerebral edema during the acute phase of RIBI. AER-271 is expected to be a promising therapeutic candidate for the treatment of RIBI by inhibiting the expression of AQP4.