intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre-clinical modelintrastriatal convection-enhanced交货导致广泛的血管周的临床前模型中的分布.pdfVIP

Barua et al. Fluids and Barriers of the CNS 2012, 9:2 FLUIDS AND BARRIERS /content/9/1/2 OF THE CNS RESEARCH Open Access Intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre- clinical model 1 2 2 2 2 3 Neil U Barua , Alison S Bienemann , Shirley Hesketh , Marcella J Wyatt , Emma Castrique , Seth Love and Steven S Gill1* Abstract Background: Convection-enhanced delivery (CED), a direct method for drug delivery to the brain through intraparenchymal microcatheters, is a promising strategy for intracerebral pharmacological therapy. By establishing a pressure gradient at the tip of the catheter, drugs can be delivered in uniform concentration throughout a large volume of interstitial fluid. However, the variables affecting perivascular distribution of drugs delivered by CED are not fully understood. The aim of this study was to determine whether the perivascular distribution of solutes delivered by CED into the striatum of rats is affected by the molecular weight of the infused agent, by co-infusion of vasodilator, alteration of infusion rates or use of a ramping regime. We also wanted to make a preliminary comparison of the distribution of solutes with that of nanoparticles. Methods: We analysed the perivascular distribution of 4, 10, 20, 70, 150 kDa fluorescein-labelled dextran and fluorescent nanoparticles at 10 min and 3 h following CED into rat striatum. We investigated the effect of local vasodilata