Abstract DP222: Microplastic Exposure Exacerbates Post-Stroke Depression and Memory Impairment

Introduction: Global plastic production and use continue to rise, with significant human health concerns. Once released into the natural environment, plastics degrade into microplastics, which can enter the human body primarily via ingestion. A recent clinical study reported that over 50% of patients undergoing carotid endarterectomy had detectable microplastics in their specimens, and their presence was associated with worse cardiovascular and cerebrovascular outcomes. However, causal links remain unclear. We compared long-term functional outcomes after acute ischemic stroke in mice with and without chronic exposure to microplastics using the middle cerebral artery occlusion model. Methods: 12-week-old male C57BL/6J mice (N = 48) were exposed to polyethylene (150 mg/kg/day), the most common polymer found in the environment and human tissues, or to vehicle for 5 weeks before stroke. Overall neurological deficit was assessed on day 28 post-stroke using the Garcia score. Cognitive and affective behaviors were evaluated with the nestlet test, elevated plus maze, open field test, and Morris water maze. To explore mechanisms, RNA sequencing of the ipsilateral hemisphere was performed on day 3 post-stroke. Results: Mice exposed to microplastics showed significantly worse Garcia score than vehicle controls ( P < 0.001; Fig. A ). Mice exposed to microplastics also had lower nestlet test scores, indicating reduced general behavior and well-being, presumably due to aggravated post-stroke depression ( P < 0.01; Fig. B ). In the elevated plus maze, mice exposed to microplastics spent less time in open arms and more time in closed arms, suggesting higher post-stroke depression ( P < 0.05, respectively; Figs. C–D ). Open field testing showed fewer entries into the center zone in mice exposed to microplastics, again indicating greater post-stroke depression ( P < 0.05; Fig. E ). In the Morris water maze, mice exposed to microplastics exhibited longer time and distance to reach the hidden platform, indicating greater post-stroke memory impairment ( P < 0.01, respectively; Figs. F–I ); the probe trial corroborated these deficits ( P < 0.05; Fig. J ). RNA sequencing revealed upregulation of pro-inflammatory genes and downregulation of genes related to neurotransmission and synaptic function in mice exposed to microplastics. Conclusions: Chronic exposure to microplastics worsens long-term neurological outcomes after stroke, exacerbating post-stroke depression and memory impairment.