关键词：大脑;药物;对立;疾病;注射(医学);磁共振成像;哺乳动物;神经,神经病学;有机磷;视网膜,症状和体征;战争
摘 要：The overall goal of this project is to determine the underlying mechanisms for the neurological symptoms associated with Gulf War Illness. The central hypothesis is that subthreshold exposures to organophosphates-OPs (defined as exposures not associated with acute signs of toxicity) may have adversely affected axonal transport and/or myelin integrity in affected individuals. We are studying two OPs, a representative insecticide that was used in the first gulf war, chlorpyrifos (CPF), and a representative, nerve agent, diisopropylfluorophosphate (DFP) in rats. The first year of this proposal has been dedicated to Specific Aim No. 1: which has been designed to evaluate OP effects on axonal transport in the living rat brain using manganese-enhanced magnetic resonance imaging (MEMRI) of the optic nerve axonal projections from the retina to the superior colliculus. The following procedures have been conducted to date (N=4-6): (1) baseline MRI scans; (2) daily injections of vehicle or chlorpyrifos (3.0-18.0 mg/kg) x 14 days; (3) a second MRI scan on the day following the last drug injection; (4) a third scan after a 4 week (OP-free) washout period. For each animal, a separate 6 hour and 24 hour scan was performed after Mg2+ eye injection. The data analyzed to date appear to support our hypothesis that repeated OP exposure leads to persistent impairments in axonal transport in the brain of living animals.