An altered blood-brain barrier contributes to brain iron accumulation and neuroinflammation in the 6-OHDA rat model of Parkinson's disease

- Possible mechanisms behind brain iron accumulation in the 6-OHDA hemiparkinsonian rat model are investigated.
- Alteration of the blood-brain barrier is detected by MRI and immunohistochemistry.
- Iron accumulation in substantia nigra is detected by MRI after BBB disruption and dopamine cell degeneration.
- Gene levels of L-ferritin are increased in substantia nigra after dopamine degeneration.
- L-ferritin, active-microglia and iron deposits are colocalized in the degenerated substantia nigra.

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.