Protection of the Blood-Brain Barrier by Pentosan Against Amyloid-β-Induced Toxicity

Endothelial cells of brain capillaries forming the blood- brain barrier play an important role in the pathogenesis and therapy of Alzheimer's disease. Amyloid- � (A�) peptides are key pathological elements in the development of the disease. A blood-brain barrier model, based on primary rat brain endothelial cells was used in which the barrier properties were induced by glial cells. The effects of amyloid peptides have been tested on cell viability and barrier functions. Ashowed toxic effects on primary rat brain endothelial cells measur ed by MTT dye conversion and the lactate dehydrogenase release. Morphologically cytoplasmic vacuolization, disruption of the structure of cytoplasmic organelles and tight junctio ns could be observed in brain endothelial cells. Treatment with A�1 42 decreased the electrical resistance, and increased the per meability of brain endothelial cell monolayers for both fluorescein an d albumin. Serum amyloid P component which stabilizes A� fibrils in cortical amyloid plaques and cerebrovascular amy loid deposits significantly potentiated the barrier-weake ning effect of A�1 42. Sulfated polysaccharide pentosan could decrease the toxic effects of Apeptides in brain endothelial cells. It could also significantly protect the barrier integrity of monolay ers from damaging actions of peptides. Pentosan modified the size, and significantly decreased the number of amyloid aggregates de monstrated by atomic force microscopy. The present data further support the toxic effects of amyloid peptides on brain endothelial cells, and can contribute to the development of molecules protecting the blood-brain barrier in Alzheimer's disease .