Measurement of blood-brain barrier permeability of rats with alpha-aminoisobutyric acid during microdialysis: Possible application to behavioral studies

The purpose of this study was to determine the suitability of alpha-aminoisobutyric acid (AIB) as a marker of the integrity of the blood-brain barrier (BBB) during studies in which amino acid content in dialysates collected by microdialysis probes and behavior of the rat are studied concurrently. AIB (200 mg/kg) was injected intraperitoneally at 1800 h into 24-h fasted, ketamine-acepromazine anesthetized rats on either 10 or 30 days following guide cannula implantation. Dialysates from the medial preoptic area and blood from the tail vein were collected 1 h before and after the AIB injection. Analysis of amino acids, including AIB, in the collections was conducted by reverse-phase HPLC. In 21 of 24 rats, AIB in dialysates averaged less than 3% of plasma at 10, 30, and 50 min after AIB injection. In those rats unidirectional blood-to-brain transfer constant, K-i, of AIB was constant and a good relationship was found between dialysate amino acid concentrations and those predicted from calculations of transport based on the brain uptake index (BUI) for some amino acids. AIB concentration in dialysates was greater than 10% of plasma at 30 min in only 3 of 24 rats. We conclude that AIB can be used as a marker to monitor the integrity of the BBB during serial measurements of dialysate concentrations of amino acids and has application in behavioral studies. (C) 1999 Elsevier Science Inc.