Department of Anatomy and Cell Biology, Chungnam National University, Daejeon, Republic of Korea.
Brain Research Institute, Chungnam National University, Daejeon, Republic of Korea.
Int J Nanomedicine. 2022 Jun 27;17:2791-2804. doi: 10.2147/IJN.S361377. eCollection 2022.
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.
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.
PER-loaded PLGA nanoparticles decreased the pro-inflammatory cytokines compared to the control group. Furthermore, they increased M2 polarization.
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.
缺血性脑卒中是全球范围内主要的致死和致残原因。此外，新生儿脑缺血是新生儿脑损伤的常见原因，导致脑瘫，进而出现学习障碍和癫痫。然而，目前针对围产期缺血性脑卒中患者，尚无有效的治疗方法。本研究旨在探讨针对小胶质细胞的帕拉米韦（PER）负载聚乳酸-羟基乙酸共聚物（PLGA）对围产期脑卒中的影响。
在 P7 大鼠通过光血栓形成形成局灶性缺血性脑卒中后，鞘内注射 PER 负载的 PLGA。评估促炎标志物（TNF-α、IL-1β、IL-6、COX2 和 iNOS）和 M2 极化标志物（Ym1 和 Arg1）。我们还研究了 PER 是否会增加体外 M2 小胶质细胞极化。
与对照组相比，PER 负载的 PLGA 纳米颗粒降低了促炎细胞因子的水平。此外，它们还增加了 M2 极化。
PER 负载的 PLGA 纳米颗粒减少了围产期缺血性脑卒中大鼠模型中的梗死面积，并改善了运动功能。与对照组相比，促炎细胞因子的水平也降低了。最后，这种针对小胶质细胞的药物递送系统的开发证实了为围产期缺血性脑卒中开发新治疗药物的潜力。
