A correlative neurobehavioral-morphological model of acrylamide neuropathy.
Sprague-Dawley rats were intoxicated with 50 mg/kg/day of acrylamide monomer given by daily intraperitoneal injections. The progression of disease was studied in intoxicated animals and unintoxicated controls using a functionally-oriented behavioral battery focusing on sensory-motor behaviors. Correlative morphological examination focused on neuronal cell bodies and nerve fibers at early time points. The results were compared with previous results from animals intoxicated with another prototype neurotoxin, 2,5-hexanedione (2,5-HD), and studied with the identical behavioral battery. With both toxins behavioral changes slightly preceded observed structural damage at the sites examined. Broadly similar behavioral patterns occurred with both toxins, i.e., more-complex functions showed the earliest deficits; hindlimb functions deteriorated before forelimb functions; grasp reflex deteriorated before place reflex. This pattern correlates with the established pattern of selective vulnerability of long and large axons. Although the patterns of behavioral toxicities were broadly similar, the functionally-oriented battery succeeded in detecting differences which corresponded with established neuropathological subtleties in the two dying-back processes. We discuss potential difficulties in correlating behavioral/clinical results with morphological data but stress the importance of such correlations.
D000178:Acrylamides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D005260:Female; D006588:Hexanones / Q000633:toxicity; D010525:Peripheral Nerves / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains
D000178:Acrylamides; D006588:Hexanones; C011269:2,5-hexanedione