BLOOD-BRAIN-BARRIER PERMEABILITY IN SENESCENT RATS

Cerebrovascular permeability to 14C-sucrose was measured in 3-mo-old and 28-mo-old conscious, restrained Fischer 344 male rats. Tracer was injected intravenously in these animals and arterial plasma concentrations were followed for 50 to 240 min, when animals were killed and regional brain radioactivity was measured. Equations derived by a two-compartment diffusion model were fit to concentration data to estimate PA (product of cerebral capillary permeability and surface area) and Ve (cerebral distribution space of 14C-sucrose). PA in 3-mo-old rats averaged 7.53 x 19-6 sec-1 in 14 cerebral regions, and was not significantly elevated in 28-mo-old rats except possibly at white matter. Ve fell from an average of 0.126 in control rats to 0.070 in 28-mo-old rats. This 45% reduction may reflect a reduced extracellular space in the older animals. The findings do not support the hypothesis that aging of the central nervous system is related to breakdown of the blood-brain barrier.