Organochlorine pesticide-related poisoning (e.g., Agent Orange and congeners) is a major lingering public health problem. The central nervous system is the principal target organ of these chemicals; the lack of an effective, direct treatment for the neurotoxicity is a major deficit. We have made several observations of key importance to this issue. (A) A chorid plexus associated system specifically transports organochlorine-type molecules from CSF and represents a potential route for their excretion from brain. (B) The choroidal system can be influenced by either nutritional or neurogenic (adrenergic) modulation. We hypothesize that brain excretion of organochlorines can be optimized by exploiting this system. Potential modulators of choroid plexus transport (with emphasis on Alpha- and Beta-adrenergic agonists, also nutritional products) will be presented under in vivo and in vitro conditions and studied for interactions with the solute 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), anionic herbicides, """"""""sharing"""""""" the organic acid carrier. Effective modulators will then be tested to see whether they alter brain excretion of the pesticide in vivo. For in vitro studies choroidal transport will be assessed by a novel assay, using scintillation spectroscopy of 14C-2,4-D or 14C-2,4,5-T and microprotein determinations on up to five tissue sections per plexus. Pharmacokinetics of 2,4-D and 2,4,5-T clearance out of CSF will be assessed in vivo. Central tissue distribution profiles of intra- ventricularly administered tracer doses of pesticide will be obtained. Electronmicroscopy and autoradiography will be done for the integrity of tissue uptake.
