Objective: This study aims to evaluate the integrity of the blood-brain barrier (BBB) in parkinsonism.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder which is accompanied by dopaminergic neuron loss and neuroinflammation, whose cause not yet been elucidated. In this context, a BBB dysfunction could be contributing to the onset or even amplifying the ongoing disease. Evans blue (EB) dye has been used as a tracer for the quantification of BBB breakdown in several neurological disorders; nevertheless, this method has not been used previously to evaluate the extension of the increasing of BBB permeability to large molecules, such as proteins, in PD.

Method: The amounts of accumulated stain in brains following injection in the jugular vein of a 2.5% solution of EB (4ml/kg of body weight) at 45 min of circulation time were evaluated in parkinsonism (unilaterally 6-OHDA-lesioned mice) and levodopa-induced dyskinesia (LID) (L-DOPA, 25mg/kg i.p.; benserazide hydrazide hydrochloride, 10 mg/kg i.p.) in C57/BL6 adult mice (6 months of age). Intravenous injection of EB in sham-operated and in saline-treated mice was also done. Afterwards, mice were killed and the brain was removed. Right and left striatum were put in formamide during 48h for dye extraction at room temperature. EB stain was measured by spectrophotometer and quantified according to a standard curve. All values obtained were corrected by background subtraction of naïve mice.

Results: EB dye concentration has been detected in the lesioned striatum from all animals, except in sham or saline-treated animals. There was no difference in parkinsonian animals (13.86 ± 8.67 ng EB / mg of tissue) and mice with LID (9.88 ± 2.98 ng EB / mg of tissue).

Conclusion: These results show that BBB dysfunction occurs independently of L-DOPA treatment in parkinsonian mice. Collectively, these data provide strong evidence of BBB breakdown in PD, which would enable the entrance of large molecules within the brain, exacerbating neuroinflammation. Acknowledgements: This work was funded by grants from The São Paulo Research Foundation (FAPESP, grant number 2018/00461-1, to FGG; and FAPESP, 2014/25029-4, to EDB) and the CNPq, grant number 402370/2016-3; and CNPq, 301639/2015-9 to EDB.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/blood-brain-barrier-breakdown-in-an-adult-mouse-model-of-parkinsons-disease/