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An altered blood–brain barrier contributes to brain iron accumulation and neuroinflammation in the 6-OHDA rat model of Parkinson's disease
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institute of Biomedical Technologies (CIBICAN), Tenerife, Spain; Department of Basic Medical Sciences, University of La Laguna, Tenerife, Spain.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). (Umeå Centre for Comparative Biology (UCCB))
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
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2017 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 362, p. 141-151Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2017. Vol. 362, p. 141-151
Keywords [en]
brain-iron, 6-OHDA, MRI, blood-brain barrier, microglia
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-142910DOI: 10.1016/j.neuroscience.2017.08.023ISI: 000412382100013PubMedID: 28842186OAI: oai:DiVA.org:umu-142910DiVA, id: diva2:1166527
Available from: 2017-12-15 Created: 2017-12-15 Last updated: 2018-06-09Bibliographically approved

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Olmedo-Díaz, SoniaOrädd, Gregeraf Bjérken, SaraMarcellino, DanielVirel, Ana

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