International Journal of Nanomedicine (Jun 2022)
Perampanel Reduces Brain Damage via Induction of M2 Microglia in a Neonatal Rat Stroke Model
Abstract
Hyo Jung Shin,1,2,* Ka Young Lee,1,3,* Joon Won Kang,4,5 Seung Gyu Choi,1,5 Dong Woon Kim,1,2,4,* Yoon Young Yi6,* 1Department of Anatomy and Cell Biology, Chungnam National University, Daejeon, Republic of Korea; 2Brain Research Institute, Chungnam National University, Daejeon, Republic of Korea; 3Department of Rehabilitation Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 4Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea; 5Department of Pediatrics, Chungnam National Hospital, School of Medicine, Chungnam National University, Daejeon, Republic of Korea; 6Department of Pediatrics, College of Medicine, Hallym University and Gangdong Sacred Heart Hospital, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Dong Woon Kim; Yoon Young Yi, Tel +82-42-580-8207 ; +82-2-2224-2251, Email [email protected]; [email protected]: 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-α, IL-1β, 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.Graphical Abstract: Keywords: ischemic stroke, neonate, poly lactic-co-glycolic acid, PLGA, nanoparticle, perampanel, microglial polarization
