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Further evidence that the blood/brain barrier impedes paraquat entry into the brain

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

PS Widdowson

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

MG Simpson

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

M. Farnworth

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

MK Ellis

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

EA Lock

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

The distribution of the non-selective herbicide paraquat was examined in the brain following subcutaneous admin istration of 20 mg kg ^-1 paraquat ion containing [¹⁴C]paraquat to male adult rats in order to determine whether paraquat crosses the blood/brain barrier. Following administration, [¹⁴C]paraquat reached a maxi mal concentration in the brain (0.05% of administered dose) within the first hour and then rapidly disappeared from the brain. However, 24 h after administration of the herbicide, about 13% of the maximal recorded concentra tion of paraquat remained in the brain (1.6 nmol g^-1 wet weight) and could not be removed by intracardiac perfu sion. Using measurements of [¹⁴C]paraquat in dissected brain regions and using quantitative autoradiography we demonstrated an asymmetrical distribution in and around the brain at 30 min (maximal concentration) and 24 h after administration. Most of the paraquat was associated with five structures, two of which, the pineal gland and linings of the cerebral ventricles lie outside the blood/brain barrier whilst the remaining three brain areas, the anterior portion of the olfactory bulb, hypothalamus and area postrema do not have a blood/brain barrier. Overall, the distribution of [¹⁴C]paraquat in the brain 24 h after systemic administration was highly correlated to the blood volume. These data indicate that any remaining paraquat in the brain 24 h after systemic administration is associated with elements of the cerebro-circulatory sys tem, such as the endothelial cells that make up the capil lary network and that there is a limited entry of paraquat into brain regions without a blood/brain barrier. No [¹⁴C]paraquat was detected in regions where there has been demonstrated pathology in brains from humans with Parkinson's disease. Finally, we could find no evidence for paraquat-induced neuronal cell necrosis 24 or 48 h after systemic administration. Overall it may be concluded that systemically administered paraquat does not pose a direct major neurotoxicological risk in the majority of brain regions which have a functional blood/brain barrier since paraquat can be excluded from the brain by this barrier.

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

Human & Experimental Toxicology, Vol. 14, No. 7, 587-594 (1995)
DOI: 10.1177/096032719501400706


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