This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Widdowson, P. Articles by Lock, E. Search for Related Content PubMed PubMed Citation Articles by Widdowson, P. Articles by Lock, E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB PARAQUAT Social Bookmarking                   What's this?

Influence of age on the passage of paraquat through the blood-brain barrier in rats: A distribution and pathological examination

Neurotoxicology Research Group, Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, UK

MJ Farnworth

Neurotoxicology Research Group, Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, UK

MG Simpson

Neurotoxicology Research Group, Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, UK

EA Lock

Neurotoxicology Research Group, Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, UK

Experiments were performed to determine the extent of paraquat entry into the brain of neonatal and elderly rats, as compared with adult rats, which may be dependent on the efficacy of the blood-brain barrier. A single, median lethal dose (20 mg/kg s.c.) of paraquat containing [¹⁴C]paraquat was administered to neonatal (10 day old), adult (3 month old) and elderly (18 month old) rats. In contrast to the adult and elderly rats where paraquat levels fell over the 24 h post-dosing period to negligible levels, paraquat concentrations in neonatal brains did not decrease with time between 0.5 and 24 h following dosing. The distribution of [¹⁴C]paraquat was measured in selective brain regions using quantitative autoradiogra phy in all three age groups of rats, 30 min and 24 h following dosing. Autoradiography demonstrated that brain paraquat distributions were similar in the rat age groups. Most of the paraquat was confined to regions outside the blood-brain barrier and to brain regions that lack a complete blood-brain barrier e.g. dorsal hypotha lamus, area postrema and the anterior olfactory bulb. Between 0.5 h and 24 h following dosing, paraquat concentrations in deeper brain structures, some distance away from the sites of entry, began to slowly increase in all the rat age groups. By 24 h following dosing, a majority of brain regions examined using quantitative autoradiogra phy revealed significantly higher paraquat concentrations in neonatal brains as compared to brain regions of adult and elderly rats. Despite increased paraquat entry into neonatal brain, we could find no evidence for paraquat- induced neuronal cell damage following a detailed histopathological examination of perfused-fixed brains. In conclusion, impaired blood-brain barrier integrity in neonatal brain thus permitting more paraquat to enter than in adult brain, did not result in neuronal damage.

Key Words: paraquat • blood-brain barrier • brain • neuropathology

Human & Experimental Toxicology, Vol. 15, No. 3, 231-236 (1996)
DOI: 10.1177/096032719601500308


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Sinha and G. S Shukla Species variation in pesticide-induced blood-brain barrier dysfunction Human and Experimental Toxicology, December 1, 2003; 22(12): 647 - 652. [Abstract] [PDF]

				M. Thiruchelvam, E. K. Richfield, R. B. Baggs, A. W. Tank, and D. A. Cory-Slechta The Nigrostriatal Dopaminergic System as a Preferential Target of Repeated Exposures to Combined Paraquat and Maneb: Implications for Parkinson's Disease J. Neurosci., December 15, 2000; 20(24): 9207 - 9214. [Abstract] [Full Text] [PDF]

				A. B. Manning-Bog, A. L. McCormack, J. Li, V. N. Uversky, A. L. Fink, and D. A. Di Monte The Herbicide Paraquat Causes Up-regulation and Aggregation of alpha -Synuclein in Mice. PARAQUAT AND alpha -SYNUCLEIN J. Biol. Chem., January 11, 2002; 277(3): 1641 - 1644. [Abstract] [Full Text] [PDF]