Conduction Velocity Distribution Reveals Fast-Fiber-Dominant Dysfunction in Acrylamide-Induced Peripheral
1Department of Biophysics, Faculty of Medicine, Izmir Bakircay University, 35665 Izmir, Türkiye.
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Background: Acrylamide (ACR) is a well-established neurotoxicant, but whether peripheral nerve dysfunction develops uniformly across all myelinated fibers or preferentially affects specific fiber subpopulations under acute high-dose exposure conditions remains unclear. This study tested the hypothesis that acute high-dose ACR exposure differentially affects fibers with distinct conduction velocities. Methods: Adult male Sprague-Dawley rats received daily intraperitoneal injections of ACR (50 mg/kg/day) or saline for 11 days, representing an acute high-dose experimental model of ACR-induced peripheral neurotoxicity. Sciatic nerves were assessed using compound action potential (CAP) recordings and conduction velocity distribution (CVD) analysis. Nerve excitability, oxidative stress markers, and histomorphometric parameters were also evaluated. Results: Acute high-dose ACR exposure induced marked body weight loss and reduced nerve excitability, reflected by increased rheobase and decreased chronaxie. CAP analysis showed significant reductions in amplitude, area, and conduction velocities. The most pronounced decrease occurred in maximum upstroke velocity, indicating preferential impairment of fast-conducting fibers. CVD analysis confirmed a marked leftward shift, with a significant reduction in fibers >50 m/s, while slower fibers were relatively preserved. These functional changes were accompanied by increased oxidative stress and supported by histomorphometric evidence of myelin and axonal alterations. Conclusions: In this acute high-dose rat model, ACR preferentially impaired fast-conducting, large-diameter myelinated fibers, revealing a fiber population-specific pattern of peripheral neurotoxicity. CVD analysis sensitively detected this selective fiber involvement, supported by structural evidence of myelin and axonal damage. These findings should be interpreted within the context of a short-duration, high-dose experimental paradigm rather than as a direct model of chronic low-level dietary or occupational exposure.
