Injury factors and pathological features of toxic milk mice during different disease stages.

OBJECTIVE: To evaluate different injury factors and pathological characteristics of the brain at different disease stages in toxic milk (TX) mice, an animal model of Wilson's disease (WD). METHODS: Thirty TX mice (10 each at 3, 6 and 12 months old) and 30 age-matched C57 mice were used in this study. Corrected phase (CP) values were determined from susceptibility-weighted images. Myelin content was determined by measuring inhibition optical density values of Luxol fast blue-stained sections. Neurofilament protein 68 kDa (NF68), ß-amyloid precursor protein (ß-APP), and myelin basic protein (MBP) levels, as well as copper and iron content, in brain nuclei of the TX mouse were evaluated. Gene amplification ratios for catalase (CAT), GSH peroxidase (GSH-PX), nitric oxide synthase (NOS), and superoxide dismutase (SOD) in mouse brain were also determined. RESULTS: Compared with C57 mice, neuronal cell counts were decreased in 12-months-old TX mice (p = .011). Myelin content was decreased in the lenticular nucleus (p = .029), thalamus (p = .030), and brainstem (p = .034) of 6-months-old TX mice; decreases in the corresponding nuclei (p = .044, .037, and .032, respectively) were also found in 12-months-old TX mice. MBP values were lower in the lenticular nucleus and thalamus (p = .027 and .016, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .24 and .040) of 12-months-old TX mice. NF-68 values were lower in the lenticular nucleus and thalamus (p = .034 and .037, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .006 and .012) of 12-months-old TX mice. ß-APP values were higher in the thalamus of 6-months-old (p = .037) and 12-months-old (p = .012) TX mice. Iron content was higher in the lenticular nucleus, thalamus, and cerebellum (p = .044, .038, and .029, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .017, .024, and .029) of 12-months-old TX mice. The NOS gene amplification multiple was higher (p = .039), whereas the SOD1 gene amplification multiple was lower (p = .041) in 12-months-old TX mice. There was no correlation between metal content or oxidation index and pathological index. CONCLUSIONS: The pathological characteristics of the brains of TX mice may differ at different ages. Different pathogenic factors, including copper and iron deposition and abnormal oxidative stress, are present at different stages.

Characterizing brain mineral deposition in patients with Wilson disease using susceptibility-weighted imaging.

AIMS: The aim of this study was to evaluate the feasibility of characterizing the brain-mineral deposition in patients with Wilson disease (WD) using susceptibility-weighted imaging (SWI). MATERIALS AND METHODS: The study enrolled 30 WD patients and 20 age-matched healthy controls. Neurological symptoms were scored using the modified Young Scale. The hepatic function indices, serum and urinary copper content, and serum iron content were determined. All study objects received the magnetic resonance imaging (MRI) and SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. The relationship between CP values and the clinical status were evaluated. RESULTS: The serum iron content of WD patients was higher than the normal. The CP values of substantia nigra, caudate nucleus, and globus pallidus of WD were lower than the normal values, while the CP value of substantia nigra was the lowest. No correlations were determined between the CP values and the iron and copper parameters. There was negative correlation between the scores of dysarthria and the CP values of the globus pallidus. There was negative correlation between the scores of tremor and the CP values of caudate nucleus. Some regions, which had high signals on T2-weighted image, had low signals on SWI. CONCLUSIONS: There might be abnormal iron metabolism in patients with WD. The decreased CP values might reflect a deposition of both copper and iron. SWI may be more sensitive than the ordinary MRI. The mineral deposition may contribute to the neural symptoms.