Neurodegeneration in thiamine deficient rats-A longitudinal MRI study.
Selective neurodegeneration accompanied by mitochondrial dysfunction characterizes neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Thiamine deficiency (TD) in rats is a model for the study of cellular and molecular mechanisms that lead to selective neuronal loss caused by chronic oxidative deficits. Neurodegeneration in TD-rats develops over a period of 12 to 14 days and can be partially reversed by thiamine administration. The aim of this study was to characterize the in-vivo progression of neurodegeneration and the neuronal rescue processes in TD using T(2) magnetic resonance mapping and diffusion tensor imaging (DTI). Each rat was scanned prior to TD induction (day 0), before the appearance of neurological symptoms (day 10), during the symptomatic stage (days 12 and 14) and during the recuperation period (days 31 and 87). Time-dependent lesions were revealed mainly in the thalamus and the inferior colliculi. Early decrease in the fractional anisotropy (FA) was found on day 10 in the inferior colliculi and to a lesser degree in the thalamus, while the earliest detectable changes in the T(2) parameter occurred only on day 12. FA values in the thalamus remained significantly low after thiamine restoration, suggesting irreversible disarrangement and replacement of neuronal structures. While T(2) values in the frontal cortex demonstrated no lesions, FA values significantly increased on days 14 and 31. An enlargement of the lateral ventricles was observed and persevered during the recovery period. This longitudinal MRI study demonstrated that in TD MRI can detect neurodegeneration and neuronal recovery. DTI is more sensitive than T(2) mapping in the early detection of TD lesions.
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel.
Vered
V
Dror
Sarah
S
Eliash
Moshe
M
Rehavi
Yaniv
Y
Assaf
Inbal E
IE
Biton
Aviva
A
Fattal-Valevski
D000704:Analysis of Variance; D000818:Animals; D016880:Anisotropy; D001931:Brain Mapping; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D007091:Image Processing, Computer-Assisted; D007245:Inferior Colliculi / Q000473:pathology* / Q000503:physiopathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000473:pathology* / Q000503:physiopathology; D013831:Thiamine / Q000008:administration & dosage; D013832:Thiamine Deficiency / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
D013831:Thiamine