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A validated quantitative method for the assessment of neuroprotective barrier impairment in neurodegenerative disease models

By Vinod Kumar, John D. Lee, Elizabeth J. Coulson, Trent M Woodruff

Posted 08 Mar 2020
bioRxiv DOI: 10.1101/2020.03.06.979930 (published DOI: 10.1111/jnc.15119)

The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are highly specialised structures that limit molecule entry from the blood, and maintain homeostasis within the central nervous system (CNS). BBB and BSCB breakdown are associated with multiple neurodegenerative diseases. Given the key role of neuroprotective barrier impairment in neurodegeneration, it is important to identify an effective quantitative method to assess barrier integrity in animal models. In the present study, we developed and validated a quantitative method for assessing BBB and BSCB integrity using sodium fluorescein, that outperformed other fluorescent dyes. We demonstrated using this method that multiple CNS regions progressively increase in permeability in models of Huntington's disease and amyotrophic lateral sclerosis, while biphasic disruption occurred in a mouse model of Alzheimer's disease with disease progression. Collectively, we report a quantitative fluorometric marker with validated reproducible experimental methods, that allows the effective assessment of BBB and BSCB integrity in animal models. This method could be useful to further the understanding of the contribution of these neuroprotective barriers to neurodegeneration processes. ### Competing Interest Statement The authors have declared no competing interest.

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