Perampanel Reduces Brain Damage via Induction of M2 Microglia in a Neonatal Rat Stroke Model

Purpose: Ischemic stroke is a leading cause of death and disability worldwide. Additionally, neonatal ischemia is a common cause of neonatal brain injury, resulting in cerebral palsy with subsequent learning disabilities and epilepsy. However, there is currently a lack of effective treatments available for patients with perinatal ischemic stroke. In this study, we investigated the effect of perampanel (PER)-loaded poly lactic-co-glycolic acid (PLGA) by targeting microglia in perinatal stroke. Methods: After formation of focal ischemic stroke by photothrombosis in P7 rats, PER-loaded PLGA was injected intrathecally. Proinflammatory markers (TNF-alpha, IL-1 beta, IL-6, COX2, and iNOS) and M2 polarization markers (Ym1 and Arg1) were evaluated. We investigated whether PER increased M2 microglial polarization in vitro. Results: PER-loaded PLGA nanoparticles decreased the pro-inflammatory cytokines compared to the control group. Furthermore, they increased M2 polarization. Conclusion: PER-loaded PLGA nanoparticles decreased the size of the infarct and increased motor function in a perinatal ischemic stroke rat model. Pro-inflammatory cytokines were also reduced compared to the control group. Finally, this development of a drug delivery system targeting microglia confirms the potential to develop new therapeutic agents for perinatal ischemic stroke.

Automated summary

Ischemic stroke and neonatal ischemia are major causes of death and disability, but current treatments for perinatal ischemic stroke are lacking. This study investigated the effects of PER-loaded PLGA nanoparticles on microglia in perinatal stroke and found that they reduced inflammation and increased cell polarization. This development of a drug delivery system targeting microglia has the potential to lead to new therapeutic agents for perinatal ischemic stroke.