RAPID BRAIN UPTAKE OF MANGANESE(II) ACROSS THE BLOOD-BRAIN-BARRIER

Mn-54(2+) uptake into brain and choroid plexus from the circulation wa s studied using the in situ rat brain perfusion technique. Initial upt ake from blood was linear with time (30 s to 6 min) and extrapolated t o zero with an average transfer coefficient of approximately 6 x 10(-5 ) ml/s/g for brain and approximately 7 x 10(-3) ml/s/g for choroid ple xus. Influx from physiologic saline was three- to fourfold more rapid and exceeded that predicted for passive diffusion by more than one ord er of magnitude. The lower uptake rate from blood could be explained b y plasma protein binding as the free fraction of Mn-54(2+) in rat plas ma was less-than-or-equal-to 30%. Purified albumin, transferrin, and a lpha2-macroglobulin were each found to bind Mn-54(2+) significantly an d to restrict brain Mn-54(2+) influx. The results demonstrate that Mn- 54(2+) is readily taken up into the CNS, most likely as the free ion, and that transport is critically affected by plasma protein binding. T he results support the hypothesis that Mn2+ transport across the blood -brain barrier is facilitated by either an active or a passive mechani sm.