title: Quantitative dual-probe microdialysis: evaluation of [3H]mannitol diffusion in agar and rat striatum.
abstract: Dual-probe microdialysis was used to study interstitial diffusion in the rat brain. A radiolabelled tracer, (3H]mannitol, was continuously infused at different concentrations via a probe acutely implanted into the striatum of an anaesthetized male rat or into a dilute agar gel. Samples were collected by a second probe placed 1 mm away from the first, and the recovered [3H]mannitol was measured by liquid scintillation counting. In the striatum, the delivery of [3H]mannitol was counteracted by its removal from the extracellular space by passive uptake into cells and clearance into the microcirculation, causing the diffusion profile to approach quasi steady-state levels within 2 h. Diffusion data from brain and agar were analysed using a mathematical model. The apparent (effective) diffusion coefficient for [3H]mannitol was D* = 2.9 x 10(-6) cm2/s, the effective volume fraction alpha* = 0.30 and the clearance rate constant kappa= 2.3 x 10(-5)/s. A tortuosity, lambda = 1.81, and penetration distance r = 4.2 mm, were calculated. We conclude that, using dual-probe microdialysis, parameters reflecting geometric and dynamic tissue properties may be obtained using appropriate mathematical analysis. Quantitative dual-probe microdialysis will be valuable in characterizing interstitial diffusion and the clearance processes underpinning volume transmission in the brain.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Höistad
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Chen
authors.forename: Charles
authors.initials: C
authors.lastname: Nicholson
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Jan
authors.initials: J
authors.lastname: Kehr
mesh_terms: D000362:Agar / Q000737:chemistry*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004058:Diffusion; D008297:Male; D008353:Mannitol / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D014316:Tritium; D008353:Mannitol; D000362:Agar