Nanoparticle-microglial interaction in the ischemic brain is modulated by injury duration and treatment.
Nanoparticle-microglial interaction in the ischemic brain is modulated by injury duration and treatment.
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DOI：
10.1002/btm2.10175
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发表时间：
2020-09
影响因子：
7.4
通讯作者：
Nance E
中科院分区：
文献类型：
--
作者：
Joseph A;Liao R;Zhang M;Helmbrecht H;McKenna M;Filteau JR;Nance E
脑缺血是新生儿和成人死亡的主要原因，目前还无法治愈。由于纳米颗粒能够克服大脑中的生物屏障，因此纳米技术代表了脑缺血治疗发展的一个有前途的领域。离体损伤模型已经成为一种高通量的替代方案，可以重现疾病过程并实现脑微环境的纳米级探测。在这项研究中，我们使用氧-葡萄糖剥夺（OGD）来模拟缺血性损伤，并研究了纳米颗粒与小胶质细胞的相互作用，小胶质细胞是大脑中的常驻免疫细胞，对治疗递送越来越感兴趣。通过测量细胞死亡和谷胱甘肽的产生，我们评估了OGD暴露时间和阿奇霉素（AZ）治疗对切片健康的影响。我们发现，0.5小时的OGD暴露和有效的治疗后，立即应用AZ一个强大的损伤反应。我们观察到OGD诱导的小胶质细胞形态向异质性和圆形增加的方向转变，以及小胶质细胞数量减少，这在治疗后逆转。OGD增强了聚苯乙烯-聚（乙二醇）（PS-PEG）纳米颗粒的扩散，改善了运输和到达靶细胞的能力。虽然小胶质细胞对树枝状聚合物或量子点（QD）的摄取在损伤后没有增强，但PS-PEG的内化显著增加。对于PS-PEG，AZ处理使小胶质细胞摄取恢复至正常对照水平。我们的研究结果表明，不同的纳米颗粒平台应在应用前仔细筛选，并在这样做时;疾病介导的脑微环境变化可以通过纳米级药物递送装置来增强细胞相互作用。
Cerebral ischemia is a major cause of death in both neonates and adults, and currently has no cure. Nanotechnology represents one promising area of therapeutic development for cerebral ischemia due to the ability of nanoparticles to overcome biological barriers in the brain. ex vivo injury models have emerged as a high‐throughput alternative that can recapitulate disease processes and enable nanoscale probing of the brain microenvironment. In this study, we used oxygen–glucose deprivation (OGD) to model ischemic injury and studied nanoparticle interaction with microglia, resident immune cells in the brain that are of increasing interest for therapeutic delivery. By measuring cell death and glutathione production, we evaluated the effect of OGD exposure time and treatment with azithromycin (AZ) on slice health. We found a robust injury response with 0.5 hr of OGD exposure and effective treatment after immediate application of AZ. We observed an OGD‐induced shift in microglial morphology toward increased heterogeneity and circularity, and a decrease in microglial number, which was reversed after treatment. OGD enhanced diffusion of polystyrene‐poly(ethylene glycol) (PS‐PEG) nanoparticles, improving transport and ability to reach target cells. While microglial uptake of dendrimers or quantum dots (QDs) was not enhanced after injury, internalization of PS‐PEG was significantly increased. For PS‐PEG, AZ treatment restored microglial uptake to normal control levels. Our results suggest that different nanoparticle platforms should be carefully screened before application and upon doing so; disease‐mediated changes in the brain microenvironment can be leveraged by nanoscale drug delivery devices for enhanced cell interaction.
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影响因子：
5.3
作者：
Fernández-Arjona MDM;Grondona JM;Granados-Durán P;Fernández-Llebrez P;López-Ávalos MD
通讯作者：
López-Ávalos MD
影响因子：
3
作者：
Fernández-López, D;Martínez-Orgado, J;Lizasoain, I
通讯作者：
Lizasoain, I
小胶质细胞和巨噬细胞在器官脑切片中由氧葡萄糖剥夺引起的脑损伤后调节细胞死亡。
影响因子：
6.2
作者：
Girard, Sylvie;Brough, David;Lopez-Castejon, Gloria;Giles, James;Rothwell, Nancy J.;Allan, Stuart M.
通讯作者：
Allan, Stuart M.
DOI：
10.1016/j.nano.2016.11.001
发表时间：
2017-04-01
影响因子：
5.4
作者：
Ducray, Angelique D.;Stojiljkovic, Ana;Mevissen, Meike
通讯作者：
Mevissen, Meike
影响因子：
2.8
作者：
de Vries, Linda S.;Groenendaal, Floris
通讯作者：
Groenendaal, Floris