Distribution of two model amino acids from cerebrospinal fluid to brain and blood.

Abstract

Ventriculocisternal perfusions of anesthetized rabbits were performed for 1-3 h with solutions containing radioactively labeled alpha-aminoisobutyric acid (AIB), cycloleucine (CYCL), and sucrose. Serial brain samples were taken at the conclusion of the perfusion period and assayed for radioactivity. Tissue concentration profiles were constructed from these data; tissue distribution spaces and diffusion coefficients (Dt) plus brain capillary transfer constants were estimated from the profiles. The Dt of sucrose was somewhat larger at 1 h than at 2 and 3 h. Tissue distribution spaces of 300-400% were found with AIB after 3 h. Inclusion of 5 mM AIB in the perfusate produced markedly lower tracer AIB spaces. The tissue distribution spaces of CYCL ranged from 100 to 400% and depended on the concentration of CYCL in the perfusate. A brain-to-blood transfer half time of 7.5 min was measured for CYCL. These findings demonstrate that sizable cellular uptake of CYCL and AIB occurs, that these processes are concentration dependent, and that the rates of influx and efflux across brain capillaries are similar.