Abstract

MICROPLASTIC NEUROTOXICITY-BBB-TARGETED PHARMACOTHERAPY

Siri Varma M.*, Kalpana P., Kavya T., Shivani Polenwar

Abstract

Microplastic and nanoplastic exposure is now a plausible biological risk due to widespread contamination of air, drinking water, and food systems. Preclinical evidence increasingly indicates that micro-/nanoplastic particles may enter systemic circulation and interact with the neurovascular unit, weakening blood–brain barrier (BBB) integrity and promoting central nervous system (CNS) injury. Proposed mechanisms include tight junction remodeling, endothelial oxidative injury, mitochondrial dysfunction, microglial activation, and NLRP3 inflammasome–driven cytokine release, which collectively undermine synaptic plasticity and behavior. Because microplastic neurotoxicity involves multiple converging pathways, a rational therapeutic strategy should integrate BBB stabilization, oxidative stress control, neuroinflammation suppression, and synaptic rescue. This review consolidates current evidence on (i) exposure routes and systemic distribution, (ii) BBB penetration and disruption mechanisms, (iii) downstream molecular cascades associated with cognitive and affective impairment, and (iv) pharmacotherapeutic countermeasures with repurposing potential, including Nacetylcysteine, minocycline, memantine, retinoid-based BBB modulators, and selective inflammasome inhibitors. Finally, research gaps and a translational roadmap are presented, emphasizing standardized particle characterization, biomarker-guided outcome assessment, and targeted studies in high-exposure occupational cohorts.

Keywords: Microplastics; Nanoplastics; Blood–Brain Barrier; Neuroinflammation; Oxidative Stress; NLRP3 Inflammasome; Drug Repurposing; Cognition; Behavior.