Neurovascular toxicity of dichlorvos: Crosstalk between endothelial dysfunction and neurodegeneration

O,O-Dimethyl O-(2,2-dichlorovinyl) phosphate (DDVP), commonly referred to as dichlorvos, is one of the most widely used organophosphorus insecticides for agricultural and domestic pest control, especially in low- and middle-income countries, due to its low cost and effectiveness. While acute neurotoxicity through the irreversible inhibition of AChE and subsequent cholinergic overstimulation is well documented, there is growing evidence that DDVP exerts broader chronic effects, particularly those involving the neurovascular system. Specifically, endothelial dysfunction and disruption of the bloodbrain barrier have been shown to be early events that link vascular injury to neurodegeneration. These databases included PubMed, Scopus, Web of Science, ScienceDirect, EMBASE, and the Toxicology Data Network. The terms used in the search included "dichlorvos," "DDVP," "organophosphate pesticide," "neurotoxicity," "endothelial dysfunction," "bloodbrain barrier," "neurodegeneration," "oxidative stress," and "crosstalk." The inclusion criterion was peer-reviewed studies published in English between 2000 and 2025, which involved in vivo and in vitro experimental studies that reported DDVP-induced neurovascular toxicity. Studies not related to DDVP, publications in languages other than English, and non-peer-reviewed sources were excluded. Studies suggest that DDVP impairs endothelial integrity through disrupting the homeostasis of oxidative stress, nitric oxide, and inflammatory signalling. This type of endothelial insult impairs selectivity in BBB permeability, enabling the infiltration of circulating toxins and cytokines into the central nervous system, thus promoting neuronal apoptosis, mitochondrial dysfunction, and neuroinflammation. These findings suggest that the neurotoxicity of DDVP extends beyond synaptic cholinergic mechanisms but includes neurovascular-crosstalk-driven degeneration. This review synthesizes current mechanistic insights into DDVP-induced neurovascular toxicity and recognizes the neurovascular unit as a critical target in organophosphate poisoning. Elucidation of the interplay between endothelial dysfunction and neuronal injury opens new avenues for risk assessment, preventive strategies, and therapeutic interventions for pesticide-related neurodegenerative disorders.