ReviewJournal of toxicology2026
Centripetal Axonal Transport as a Gateway to the CNS for Veterinary Antiparasitics: Bypassing the Blood-Brain Barrier, Clinical Impact in Vulnerable Age Groups, and the Potential Facilitating Role of PFAS.
Review in Journal of toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The widespread use of veterinary antiparasitics, including neonicotinoids, isoxazolines, avermectins, and pyrethroids, is essential for canine health but raises concerns regarding potential neurotoxicity, particularly in young and geriatric animals. While the blood-brain barrier (BBB) offers significant protection, this review confronts a central "Safety Paradox": how can a drug class with a demonstrated high therapeutic index in conventional safety studies be associated with a significant and persistent number of real-world neurological adverse events? We propose that centripetal (retrograde) axonal transport represents a critical, underappreciated pathway for these compounds to access the central nervous system (CNS) from peripheral nerve terminals, offering a mechanistic solution to this paradox. This mechanism, well documented for various toxins and pathogens, could allow antiparasitics to bypass the BBB, leading to direct neuronal effects and contributing to clinical signs such as tremors. We review the neurotoxic mechanisms of these common antiparasitics, the established principles of retrograde axonal transport, and the chemical properties that make them candidates for such transport. Furthermore, we introduce the expanded hypothesis that per- and polyfluoroalkyl substances (PFASs)-present not only as "inert" ingredients or contaminants but, as recent regulatory findings reveal, also as active ingredients themselves-could act as both facilitators of transport for other neurotoxicants and as direct, cotransported neurotoxic agents. This review synthesizes existing and recent evidence to build a compelling case for axonal transport as a significant contributor to antiparasitic neurotoxicity, discusses its potential for differential clinical impact in young and old dogs, and highlights the urgent need for research into this pathway and the complex toxicological role of formulation components like PFAS.
Indexed as
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.