FURTHER EVIDENCE THAT THE BLOOD-BRAIN-BARRIER IMPEDES PARAQUAT ENTRY INTO THE BRAIN

The distribution of the non-selective herbicide paraquat was examined in the brain following subcutaneous administration of 20 mg kg(-1) par aquat ion containing [C-14]paraquat to male adult rats in order to det ermine whether paraquat crosses the blood/brain barrier. Following adm inistration, [C-14]paraquat reached a maximal concentration in the bra in (0.05% of administered dose) within the first hour and then rapidly disappeared from the brain. However, 24 h alter administration of the herbicide, about 13% of the maximal recorded concentration of paraqua t remained in the brain (1.6 nnol g(-1) wet weight) and could not be r emoved by intracardiac perfusion. Using measurements of [C-14]paraquat in dissected brain regions and using quantitative autoradiography we demonstrated an asymmetrical distribution in and around the brain at 3 0 min (maximal concentration) and 24 h after administration. Most of t he paraquat was associated with five structures, two of which, the pin eal gland and linings of the cerebral ventricles lie outside the blood /brain barrier whilst the remaining three brain areas, the anterior po rtion of the olfactory bulb, hypothalamus and area postrema do not hav e a blood/brain barrier. Overall, the distribution of [C-14]paraquat i n the brain 24 h after systemic administration was highly correlated t o the blood volume. These data indicate that any remaining paraquat in the brain 24 h after systemic administration is associated with eleme nts of the cerebro-circulatory system, such as the endothelial cells t hat make up the capillary network and that there is a limited entry of paraquat into brain regions without a blood/brain barrier. No [C-14]p araquat was detected in regions where there has been demonstrated path ology in brains from humans with Parkinson's disease. Finally, we coul d find no evidence for paraquat-induced neuronal cell necrosis 24 or 4 8 h after systemic administration. Overall it may be concluded that sy stemically administered paraquat does not pose a direct major neurotox icological risk in the majority of brain regions which have a function al blood/brain barrier since paraquat can be excluded from the brain b y this barrier.