Functional Study of Blood-Brain Barrier in Neurotransplanted Patients

Several investigators have studied abnormal free amino acid concentrations in Parkinson’s disease (PD) cerebrospinal fluid (CSF). Clearly, the detection of amino acids in CSF and the determination of whether the blood-brain barrier (BBB) is altered in subjects that received transplants of neural tissue by open surgical methods would contribute to our knowledge of the role of these parameters in cerebral transplantation. Employing automated ion exchange chromatographic techniques, we report in this article measurements of 32 amino compounds in CSF obtained before and after brain transplants in 9 patients (6 males and 3 females) with PD grade III-IV (Hohen and Yahr rating scale), a mean age of 47.2 years, and a mean evolution time of 12.3 years. We also measured CSF and serum concentrations of albumin and IgG by radial immunodiffusion in 4 of these neurotransplanted patients. The parkinsonian group showed high levels of some amino acids in CSF including leucine, tyrosine (precursor of dopamine), lysine and arginine when compared with the control group. CSF amino acid levels were elevated through 12 weeks after surgery and some of them remained elevated through 24 weeks of postoperative measurements in five of the six patients. These amino acids were present in both plasma and CSF and the concentration in plasma was 6.5 to 12.3 times greater than that in CSF. These data suggest that there might be a persistent limited defect in the BBB to lowmolecular weight molecules following fetal-brain transplantation. A tendency toward higher albumin quotient values [(CSF albumin)/(serum albumin)/1000] and IgG quotient values [(CSF IgG)/(serum IgG)/1000] was present 4 weeks after transplant in all studied cases. In two of these patients, incremented albumin and IgG quotient values were marked, indicating increased passage of albumin and IgG across the BBB. To summarize, levels of albumin and IgG quotients post-transplantation as compared with before transplantation showed a tendency to increase for 4 weeks after surgery. Small molecules such as amino acids appeared to cross the BBB more readily 24 weeks following surgery in at least some patients. Physiopathological effects of increased BBB permeability to amino acids are not known. Future studies in animal models are necessary.