|Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Taken together with clinical findings that blood-brain barrier (BBB) damages contribute to the progress of neurodegenerative disease such as Creutzfeld-Jacob's disease and Alzheimer's disease, as pentosan polysulfate (PPS) prevents a PrP106-126 (neurotoxic peptide of prion protein)-induced damage of brain capillary endothelial cells (BBB cells), it is postulated that PPS is an anti-dementia drug. In this research project, we investigated the effect of PPS on BBB functions, by using 1) our newly developed in vitro model of the BBB kit constructed with three types of cell ; rat BBB cells, pericytes, and astrocytes, 2) GP8 immortalized rat brain endothelial cells, and 3) in vitro model of delayed neuronal death of SHRSP. PPS (20-200 μg/ml) coincubated with cells in BBB kit for 60 min increased transendothelial electrical resistance, and decreased permeabilities of sodium fluorescein and Evans' blue-albumin. In GP8 cells, treatment with amyloid Aβ peptide fragment 25-35, I-40, and PrP106-126 resulted in an endothelial toxicity. Incubation of GP8 cells with 100 μM PrP106-126 for 24 h decreased mRNA expression of mdrla gene. PPS attenuated both morphological and functional damages caused by amyloid-, and PrP106-123 peptides treatment. PPS, when given intraperitoneally 10 min after the transient forbrain ischemia, delayed the onset of ischemia-related delayed neuronal death of the hippocampus CA1 pyramidal cells of SHRSP. Thus, the possibility that PPS has a therapeutic potential in the treatment of BBB damages as an anti-dementia drug would have to be considered.