Blood-brain barrier damage and brain penetration of antiepileptic drugs: role of serum proteins and brain edema.
Regional cerebrovascular permeability-surface area (PA) products were calculated for two nonelectrolyte tracers differing considerably in molecular weight and size [( 14C]sucrose: mol wt 340 daltons, radius 5 A; and [3H]dextran: mol wt approximately 79,000 daltons, radius approximately 65 A) in control (uninfused) rats and in rats 6, 35, and 55 min after the blood-brain barrier was opened by a 30-s infusion of 1.8 molal L(+)-arabinose into a carotid artery. In control brain regions, mean PA for [14C]sucrose was 10(-5) s-1, whereas PA was not measurable for [3H]dextran. Six minutes after arabinose infusion, PA for both substances increased dramatically to 10(-4) s-1 or more; PA then declined at 35 and 55 min after arabinose infusion, but more markedly for [3H]dextran than for [14C]sucrose. The results demonstrate a size-dependent, differential rate of closure of the blood-brain barrier after osmotic opening. This is shown to be consistent with a pore model with bulk flow for blood-brain barrier permeability after osmotic opening.