[Age-related changes in the blood-brain barrier in the rat with reference to methionine, lysine, glutamic acid and N-methyl-N-nitrosourea]

One possible cause of the decline in brain function with aging might be an age-related change in the blood-brain barrier (BBB). Therefore, we assessed the "Brain Uptake Index" (BUI) by the method of Oldendorf (1970) in 99 male Sprague-Dawley rats aged 3-4 months (young), 7-11 months (adult) and 28-31 months (old) for the following compounds: methionine, lysine, glutamic acid and N-methyl-N-nitrosourea (MNU). The BUIs of methionine and MNU showed marked but contrasting biphasic changes with age: the adult animals had the highest BUIs for methionine and the lowest for MNU, compared with the young and old groups. With lysine, a declining tendency with age was indicated, whereas no differences could be detected with glutamic acid. The results suggest that the BBB undergoes different changes in development and aging, leading to an optimal amino acid transport and minimum penetration of lipophilic agents (MNU) in the adult brain. Thereafter, the opposite takes place, reducing necessary transport and increasing the penetration of lipophilic compounds.