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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\u2010throughput alternative that can recapitulate disease processes and enable nanoscale probing of the brain microenvironment. In this study, we used oxygen\u2013glucose 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\u2010induced 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\u2010poly(ethylene glycol) (PS\u2010PEG) 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\u2010PEG was significantly increased. For PS\u2010PEG, 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\u2010mediated changes in the brain microenvironment can be leveraged by nanoscale drug delivery devices for enhanced cell interaction.<\/jats:p>","DOI":"10.1002\/btm2.10175","type":"journal-article","created":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T03:39:39Z","timestamp":1596253179000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Nanoparticle\u2010microglial interaction in the ischemic brain is modulated by injury duration and treatment"],"prefix":"10.1002","volume":"5","author":[{"given":"Andrea","family":"Joseph","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering University of Washington  Seattle Washington 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