Uptake of Exogenous Glutamate and Aspartate by Circumventricular Organs but Not Other Regions of Brain

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Abstract
Glutamate (Glu) and aspartate (Asp) concentrations in blood and selected regions of brain were measured at sequential intervals over a 3-h period following subcutaneous administration of Glu, Asp, or Glu plus Asp (2 mg/g body wt) to 4-day-old mouse or rat pups. Marked serum elevations of the administered amino acids (peak values exceeding 200 times control levels) were detected within 1 h. In circumventricular organ (CVO) regions of brain, which are thought to have no blood-brain barriers, a sharp and steady increase in tissue concentrations of the administered amino acids (peak values 4–10 times higher than control levels) occurred during a 15–120 min interval, whereas no appreciable increases were detected in other brain regions. When 2 mg/g Glu plus 2 mg/g Asp were administered, CVO tissue concentrations of each amino acid rose to approximately the same level obtained when the individual amino acids were given. It is concluded that blood-brain barriers preventing net entry of Glu or Asp into brain proper are relatively well established by the 4th postnatal day in rodents, but that CVO brain regions lack such barriers; selective access of blood-borne Glu or Asp to CVO neurons explains why these neurons are selectively destroyed by systemic administration of these neurotoxic amino acids.