MRI studies of the neurotoxic effects of l-2-chloropropionic acid on rat brain

Abstract

l-2-Chloropropionic acid (l-CPA) is selectively toxic to rat cerebellar granule cells; necrosis is first observed about 36 hours after administration of l-CPA (750 mg/kg p.o.) becoming more marked by 48 h. Parallel to the onset of cell death an increase in cerebellar water content and sodium concentration has been reported suggesting an oedematous reaction. In this study T2-weighted (T2WI) and diffusion weighted (DWI) imaging were used to detect the development of neuronal damage in the cerebellum of rats as a result of exposure to l-CPA. T2WI and DWI were not able to detect cerebellar abnormalities at 37 h post-dosing except for a slight swelling of the cerebellum. However, at 48 h post-dosing when cerebellar swelling and granule cell necrosis were marked, T2WI and DWI hyperintensities were observed in the cerebellum. Therefore, under the conditions of this study, MRI was not able to detect abnormalities in the cerebellum prior to the onset of the clinical signs of neurotoxicity or at the time of early histological changes. T2WI also suggested a marked increase in the amount of fluid in the ventricular system of rats 37 and 48 h after dosing; fluid accumulation was observed in all animals studied whether or not necrosis was detected. The occurrence of T2WI hyperintensity in the forebrain lead us to discover a new lesion in the habenular nucleus.