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Magnetic resonance imaging (MRI) to study striatal iron accumulation in a rat model of Parkinson's disease.

Virel A, Faergemann E, Orädd G, Strömberg I - PLoS ONE (2014)

Bottom Line: The results revealed that in comparison with control animals, injection of 6-OHDA into the rat striatum provoked an edematous process, visible in T2-weighted images that was accompanied by an accumulation of iron clearly detectable in T2*-weighted images.Furthermore, Prussian blue staining to detect iron in sectioned brains confirmed the existence of accumulated iron in the areas of T2* hypointensities.The presence of ED1-positive microglia in the lesioned striatum overlapped with this accumulation of iron, indicating areas of toxicity and loss of dopamine nerve fibers.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.

ABSTRACT
Abnormal accumulation of iron is observed in neurodegenerative disorders. In Parkinson's disease, an excess of iron has been demonstrated in different structures of the basal ganglia and is suggested to be involved in the pathogenesis of the disease. Using the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease, the edematous effect of 6-OHDA and its relation with striatal iron accumulation was examined utilizing in vivo magnetic resonance imaging (MRI). The results revealed that in comparison with control animals, injection of 6-OHDA into the rat striatum provoked an edematous process, visible in T2-weighted images that was accompanied by an accumulation of iron clearly detectable in T2*-weighted images. Furthermore, Prussian blue staining to detect iron in sectioned brains confirmed the existence of accumulated iron in the areas of T2* hypointensities. The presence of ED1-positive microglia in the lesioned striatum overlapped with this accumulation of iron, indicating areas of toxicity and loss of dopamine nerve fibers. Correlation analyses demonstrated a direct relation between the hyperintensities caused by the edema and the hypointensities caused by the accumulation of iron.

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Correlations between edema and iron accumulation.A) Regression line showing the correlation between hyperintensities at day 2 and corresponding hypointensities at 4 weeks for different positions in the striatum (data points = 1.2 0.6, 0, −0.6, −1.2 mm from injection) of 6-OHDA injected animals. B) Regression line showing the correlation between total hyperintense areas at day 2 and corresponding hypointense areas at 4 weeks, calculated from control, and 6-OHDA groups (represented by blue and white dots respectively).
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pone-0112941-g005: Correlations between edema and iron accumulation.A) Regression line showing the correlation between hyperintensities at day 2 and corresponding hypointensities at 4 weeks for different positions in the striatum (data points = 1.2 0.6, 0, −0.6, −1.2 mm from injection) of 6-OHDA injected animals. B) Regression line showing the correlation between total hyperintense areas at day 2 and corresponding hypointense areas at 4 weeks, calculated from control, and 6-OHDA groups (represented by blue and white dots respectively).

Mentions: To demonstrate the correlation between edema and iron deposition, correlation and linear regression analyses were performed (Fig. 5). A first correlation analysis was performed to study the relation between edema and iron accumulation at different positions from the injection area. In 6-OHDA-lesioned animals, for each distance (1.2, 0.6, 0.0, −0.6, −1.2 mm from the injection site), mean hyperintense values at two days were plotted against the corresponding hypointense values at 4 weeks (Fig. 5A). Correlation for the data revealed that hypointensities and hyperintensities in the 6-OHDA were significantly related, (r = 0.92, p<0.05, two tailed). Additionally, total hyperintensities at two days were calculated for each animal in the study (control and 6-OHDA injected) and plotted against total hypointense values from the same animals at 4 weeks (Fig. 5B). The data revealed that total hypointensities and hyperintensities were correlated (r = 0.95, p<0.001 two tailed). Animals with high hyperintense values coincided with high hypointense values and vice versa.


Magnetic resonance imaging (MRI) to study striatal iron accumulation in a rat model of Parkinson's disease.

Virel A, Faergemann E, Orädd G, Strömberg I - PLoS ONE (2014)

Correlations between edema and iron accumulation.A) Regression line showing the correlation between hyperintensities at day 2 and corresponding hypointensities at 4 weeks for different positions in the striatum (data points = 1.2 0.6, 0, −0.6, −1.2 mm from injection) of 6-OHDA injected animals. B) Regression line showing the correlation between total hyperintense areas at day 2 and corresponding hypointense areas at 4 weeks, calculated from control, and 6-OHDA groups (represented by blue and white dots respectively).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232582&req=5

pone-0112941-g005: Correlations between edema and iron accumulation.A) Regression line showing the correlation between hyperintensities at day 2 and corresponding hypointensities at 4 weeks for different positions in the striatum (data points = 1.2 0.6, 0, −0.6, −1.2 mm from injection) of 6-OHDA injected animals. B) Regression line showing the correlation between total hyperintense areas at day 2 and corresponding hypointense areas at 4 weeks, calculated from control, and 6-OHDA groups (represented by blue and white dots respectively).
Mentions: To demonstrate the correlation between edema and iron deposition, correlation and linear regression analyses were performed (Fig. 5). A first correlation analysis was performed to study the relation between edema and iron accumulation at different positions from the injection area. In 6-OHDA-lesioned animals, for each distance (1.2, 0.6, 0.0, −0.6, −1.2 mm from the injection site), mean hyperintense values at two days were plotted against the corresponding hypointense values at 4 weeks (Fig. 5A). Correlation for the data revealed that hypointensities and hyperintensities in the 6-OHDA were significantly related, (r = 0.92, p<0.05, two tailed). Additionally, total hyperintensities at two days were calculated for each animal in the study (control and 6-OHDA injected) and plotted against total hypointense values from the same animals at 4 weeks (Fig. 5B). The data revealed that total hypointensities and hyperintensities were correlated (r = 0.95, p<0.001 two tailed). Animals with high hyperintense values coincided with high hypointense values and vice versa.

Bottom Line: The results revealed that in comparison with control animals, injection of 6-OHDA into the rat striatum provoked an edematous process, visible in T2-weighted images that was accompanied by an accumulation of iron clearly detectable in T2*-weighted images.Furthermore, Prussian blue staining to detect iron in sectioned brains confirmed the existence of accumulated iron in the areas of T2* hypointensities.The presence of ED1-positive microglia in the lesioned striatum overlapped with this accumulation of iron, indicating areas of toxicity and loss of dopamine nerve fibers.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.

ABSTRACT
Abnormal accumulation of iron is observed in neurodegenerative disorders. In Parkinson's disease, an excess of iron has been demonstrated in different structures of the basal ganglia and is suggested to be involved in the pathogenesis of the disease. Using the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease, the edematous effect of 6-OHDA and its relation with striatal iron accumulation was examined utilizing in vivo magnetic resonance imaging (MRI). The results revealed that in comparison with control animals, injection of 6-OHDA into the rat striatum provoked an edematous process, visible in T2-weighted images that was accompanied by an accumulation of iron clearly detectable in T2*-weighted images. Furthermore, Prussian blue staining to detect iron in sectioned brains confirmed the existence of accumulated iron in the areas of T2* hypointensities. The presence of ED1-positive microglia in the lesioned striatum overlapped with this accumulation of iron, indicating areas of toxicity and loss of dopamine nerve fibers. Correlation analyses demonstrated a direct relation between the hyperintensities caused by the edema and the hypointensities caused by the accumulation of iron.

Show MeSH
Related in: MedlinePlus