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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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Histological analysis of hypointense areas.Prussian blue staining combined with ED1-inmunoreativity at 2 days postlesion (A, B, E, F) shows that in 6-OHDA injected animals (A, B) and control animals (E, F) iron (A and E) and microglia (B and F) are almost absent. At 4 weeks in 6-OHDA animals (C, D) the iron deposits are located to the same areas as active microglia (D). In control animals accumulation of iron (G) and activation of microglia (H) was less pronounced. Arrows show ED1-negative cells that were iron positive. Scale bar 50 µm.
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pone-0112941-g006: Histological analysis of hypointense areas.Prussian blue staining combined with ED1-inmunoreativity at 2 days postlesion (A, B, E, F) shows that in 6-OHDA injected animals (A, B) and control animals (E, F) iron (A and E) and microglia (B and F) are almost absent. At 4 weeks in 6-OHDA animals (C, D) the iron deposits are located to the same areas as active microglia (D). In control animals accumulation of iron (G) and activation of microglia (H) was less pronounced. Arrows show ED1-negative cells that were iron positive. Scale bar 50 µm.

Mentions: Histological Prussian blue staining of the perfused brains (control and 6-OHDA) followed by ED1 staining was performed at 2 days (Fig. 6 A, B, E, F) or 4 weeks (Fig. 6 C, D, G, H) postinjection. The results revealed that at 2 days postlesion no iron was seen in 6-OHDA animals (Fig. 6 A) or in control animals (Fig. 6E) and only a small microglia reaction was detected (Fig. 6 B, F). On the other hand, at 4 weeks postlesion, a strong accumulation of iron was seen in the 6-OHDA injected animals (Fig. 6 C) compared with control animals (Fig. 6 G). At this time point ED1 imunohistochemistry showed a strong accumulation of reactive microglia in the center of the lesioned area, which was less pronounced in control animals (Figs. 6 D and H respectively). Most of ED1-positive cells overlapped with Prussian blue-positive deposits. However, other cells than ED1-positive microglia were positive for iron (Fig. 6, arrows). The presence of iron at four weeks was correlated with the T2* hypointensities observed at different distances from the injection of 6-OHDA (Fig. 7A, B, C). In control animals the presence of iron was almost absent (Fig. 7 D, E) which accordingly also coincided with the absence of hypointensities in these animals.


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)

Histological analysis of hypointense areas.Prussian blue staining combined with ED1-inmunoreativity at 2 days postlesion (A, B, E, F) shows that in 6-OHDA injected animals (A, B) and control animals (E, F) iron (A and E) and microglia (B and F) are almost absent. At 4 weeks in 6-OHDA animals (C, D) the iron deposits are located to the same areas as active microglia (D). In control animals accumulation of iron (G) and activation of microglia (H) was less pronounced. Arrows show ED1-negative cells that were iron positive. Scale bar 50 µm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4232582&req=5

pone-0112941-g006: Histological analysis of hypointense areas.Prussian blue staining combined with ED1-inmunoreativity at 2 days postlesion (A, B, E, F) shows that in 6-OHDA injected animals (A, B) and control animals (E, F) iron (A and E) and microglia (B and F) are almost absent. At 4 weeks in 6-OHDA animals (C, D) the iron deposits are located to the same areas as active microglia (D). In control animals accumulation of iron (G) and activation of microglia (H) was less pronounced. Arrows show ED1-negative cells that were iron positive. Scale bar 50 µm.
Mentions: Histological Prussian blue staining of the perfused brains (control and 6-OHDA) followed by ED1 staining was performed at 2 days (Fig. 6 A, B, E, F) or 4 weeks (Fig. 6 C, D, G, H) postinjection. The results revealed that at 2 days postlesion no iron was seen in 6-OHDA animals (Fig. 6 A) or in control animals (Fig. 6E) and only a small microglia reaction was detected (Fig. 6 B, F). On the other hand, at 4 weeks postlesion, a strong accumulation of iron was seen in the 6-OHDA injected animals (Fig. 6 C) compared with control animals (Fig. 6 G). At this time point ED1 imunohistochemistry showed a strong accumulation of reactive microglia in the center of the lesioned area, which was less pronounced in control animals (Figs. 6 D and H respectively). Most of ED1-positive cells overlapped with Prussian blue-positive deposits. However, other cells than ED1-positive microglia were positive for iron (Fig. 6, arrows). The presence of iron at four weeks was correlated with the T2* hypointensities observed at different distances from the injection of 6-OHDA (Fig. 7A, B, C). In control animals the presence of iron was almost absent (Fig. 7 D, E) which accordingly also coincided with the absence of hypointensities in these animals.

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