Micro- and Nanoplastics in the Human Brain: Mechanistic Plausibility, Translational Challenges, and Links to...

The exponential growth in plastic production since the mid-twentieth century has led to the pervasive presence of micro- and nanoplastics (MNPs) across ecosystems and human exposure pathways, coinciding with a rising global burden of neurological disorders. Increasing evidence demonstrates that MNPs are not confined to peripheral tissues but can accumulate even in the human brain, raising concerns about their potential contribution to neurological disease. This structured review synthesizes global trends in plastic production, environmental MNP burden, and human exposure, together with emerging data on brain accumulation, entry pathways, neurotoxic mechanisms, and key translational challenges. We present evidence showing that MNPs may cross brain barriers via multiple routes, including the blood-brain barrier, blood-cerebrospinal fluid barrier, olfactory, and circumventricular pathways, particularly under conditions of barrier vulnerability. Experimental studies reveal that once in neural tissue, MNPs may disrupt synaptic function, mitochondrial homeostasis, autophagy, and redox balance, while activating neuroinflammatory and gut-brain axis-mediated pathways. These mechanisms intersect with disease-relevant processes implicated in multiple neurological disorders whose global prevalence and societal burden have sharply increased over recent decades, including stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, mood disorders, and neurodevelopmental conditions. Despite growing mechanistic plausibility, translational and human epidemiological evidence remains limited by methodological heterogeneity, a lack of standardized detection methods, and the absence of longitudinal clinical data/studies. We highlight critical analytical and translational gaps, public health implications, and priorities for longitudinal, biomarker‑driven studies needed to rigorously test whether MNPs may contribute to population‑level risk of neurological disease.