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

L-2-Chloropropionic acid (L-CPA) is selectively toxic to rat cerebellar gra nule 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 ons et of cell death an increase in cerebellar water content and sodium concent ration has been reported suggesting an oedematous reaction. In this study T -2-weighted (T2WI) and diffusion weighted (DWI) imaging were used to detect the development of neuronal damage in the cerebellum of rats as a result o f exposure to L-CPA. T2WI and DWI were not able to detect cerebellar abnorm alities 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 necr osis were marked, T2WI and DWI hyperintensities were observed in the cerebe llum. Therefore, under the conditions of this study, MRI was not able to de tect abnormalities in the cerebellum prior to the onset of the clinical sig ns of neurotoxicity or at the time of early histological changes. T2WI also suggested a marked increase in the amount of fluid in the ventricular syst em 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 T2 WI hyperintensity in the forebrain lead us to discover a new lesion in the habenular nucleus. (C) 2001 Elsevier Science Inc. All rights reserved.