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  • 1.
    Olmedo-Díaz, Sonia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Estévez-Silva, Héctor
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Institute of Biomedical Technologies (CIBICAN), Tenerife, Spain; Department of Basic Medical Sciences, University of La Laguna, Tenerife, Spain.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    af Bjérken, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Marcellino, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Institute of Biomedical Technologies (CIBICAN), Tenerife, Spain.
    Virel, Ana
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    An altered blood–brain barrier contributes to brain iron accumulation and neuroinflammation in the 6-OHDA rat model of Parkinson's disease2017Ingår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 362, s. 141-151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Brain iron accumulation is a common feature shared by several neurodegenerative disorders including Parkinson's disease. However, what produces this accumulation of iron is still unknown. In this study, the 6-hydroxydopamine (6-OHDA) hemi-parkinsonian rat model was used to investigate abnormal iron accumulation in substantia nigra. We investigated three possible causes of iron accumulation; a compromised blood-brain barrier (BBB), abnormal expression of ferritin, and neuroinflammation. We identified alterations in the BBB subsequent to the injection of 6-OHDA using gadolinium-enhanced magnetic resonance imaging (MRI). Moreover, detection of extravasated IgG suggested that peripheral components are able to enter the brain through a leaky BBB. Presence of iron following dopamine cell degeneration was studied by MRI, which revealed hypointense signals in the substantia nigra. The presence of iron deposits was further validated in histological evaluations. Furthermore, iron inclusions were closely associated with active microglia and with increased levels of L-ferritin indicating a putative role for microglia and L-ferritin in brain iron accumulation and dopamine neurodegeneration.

  • 2.
    Virel, Ana
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Rehnmark, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Olmedo-Diaz, Sonia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Faergemann, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Magnetic resonance imaging as a tool to image neuroinflammation in a rat model of Parkinson's disease: phagocyte influx to the brain is promoted by bilberry-enriched diet2015Ingår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 42, nr 10, s. 2761-2771Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neuroinflammation is a chronic event in neurodegenerative disorders. In the rat model of Parkinson's disease, including a striatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA), antioxidant treatment affects the inflammatory process. Despite a heavy accumulation of microglia early after the injury, dopamine nerve fibre regeneration occurs. It remains unclear why this heavy accumulation of microglia is found early after the lesion in antioxidant-treated animals, or even more, what is the origin of these microglia. In this study magnetic resonance imaging (MRI) was used to elucidate whether the inflammatory response was generated from the blood or from activated brain microglia. Superparamagnetic iron oxide (SPIO) nanoparticles were injected intravenously prior to a striatal 6-OHDA injection to tag phagocytes in the blood. Rats were fed either with bilberry-enriched or control diet. T2*-weighted MRI scans were performed 1 week after the lesion, and hypointense areas were calculated from T2*-weighted images, to monitor the presence of SPIO particles. The results revealed that feeding the animals with bilberries significantly promoted accumulation of blood-derived immune cells. Gadolinium-enhanced MRI demonstrated no difference in leakage of the blood-brain barrier independent of diets. To conclude, bilberry-enriched diet promotes an influx of periphery-derived immune cells to the brain early after injury.

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