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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 universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
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.
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). (Umeå Centre for Comparative Biology (UCCB))
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
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2017 (Engelska)Ingår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 362, s. 141-151Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2017. Vol. 362, s. 141-151
Nyckelord [en]
brain-iron, 6-OHDA, MRI, blood-brain barrier, microglia
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-142910DOI: 10.1016/j.neuroscience.2017.08.023ISI: 000412382100013PubMedID: 28842186Scopus ID: 2-s2.0-85028954543OAI: oai:DiVA.org:umu-142910DiVA, id: diva2:1166527
Tillgänglig från: 2017-12-15 Skapad: 2017-12-15 Senast uppdaterad: 2023-03-23Bibliografiskt granskad

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

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