Intranasal administration of edaravone attenuates brain injury by targeting neuroinflammation and oxidative stress following intracerebral hemorrhage in mice

Background

Intracerebral hemorrhage (ICH) poses a significant global health burden, characterized by high mortality rates and long-term disability. Despite advancements in stroke management, effective therapeutic strategies targeting secondary brain injury mechanisms post-ICH remain elusive. In this study, we explored the neuroprotective potential of edaravone (EDA) in a mouse model of ICH, with particular focus on the innovative approach of intranasal administration.

Methods

A total of 96 C57BL/6 mice were randomly assigned to sham group (n ​= ​32), ICH ​+ ​vehicle group (n ​= ​32) and ICH ​+ ​EDA group (n ​= ​32). ICH was induced using 0.5 ​μL bacterial collagenase VII. EDA (3 ​mg/kg) was administered intranasally starting 2 ​h after ICH and every 12 ​h thereafter (20 ​μL per mouse; 5 ​μL per nostril every 5 ​min). The ICH ​+ ​vehicle group received the identical solvent at an equivalent volume as the EDA group via intranasal administration. We evaluated neurological functions through mNSS, corner turn, and forelimb placement tests. Additionally, brain water content, immunofluorescence staining, western blot analysis, Evans blue extravasation assay, and TUNEL staining were utilized to examine the neuroprotective effects of EDA in ICH.

Results

Our findings demonstrate that intranasal delivery of EDA significantly alleviated neurological deficits and reduced brain injury following ICH. This was evidenced by improvements in behavioral assessments, decreased brain water content, reduced lesion volume, and diminished cell death in the perihematomal region. Notably, intranasal EDA administration preserved blood-brain barrier integrity, suppressed microglia/macrophage activation, and mitigated oxidative stress, highlighting its multifaceted neuroprotective mechanisms.

Conclusion

These outcomes underscore the therapeutic promise of intranasal administration of EDA as a prospective intervention for alleviating secondary brain injury post-ICH and advocate for further translational and clinical investigations to validate its efficacy and safety in ICH patients.