title: Cerebrospinal fluid indices of blood-brain barrier permeability following adrenal-brain transplantation in patients with Parkinson's disease.
abstract: Cerebrospinal fluid (CSF) and serum or plasma concentrations of albumin, IgG and carbidopa were measured before and after adrenal-brain transplantation in patients with Parkinson's disease to indirectly assess blood-brain barrier (BBB) integrity. Previous studies in animals have suggested that the BBB is compromised by cerebral transplantation. CSF and plasma levodopa was also measured to permit comparison with the carbidopa values, recognizing that levodopa readily crosses the BBB via facilitated transport. Our patients underwent adrenal-brain transplantation in accordance with the method of Madrazo et al. (I. Madrazo, R. Drucker-Colin, V. Diaz, J. Martinez-Mata, C. Torres, and J. J. Becerril, 1987, N. Engl. J. Med. 316: 831-834) in which adrenal medullary pieces are implanted in the head of the caudate nucleus, in contact with the cerebrospinal fluid. All patients were maintained on oral carbidopa/levodopa therapy after surgery. CSF albumin/serum albumin and CSF IgG/serum IgG ratios were initially elevated above the preoperative baseline 6 weeks after the surgery; however, these values returned to the preoperative baseline by 6 months following the operation in six of seven patients. This suggested that the BBB was sufficiently intact to exclude these larger protein molecules from the CSF of these six patients. On the other hand, exogenously administered carbidopa, which normally is largely excluded from the cerebrospinal fluid by the BBB, was modestly increased in the CSF in four of the five patients in which it was measured. This suggests that the transplant BBB might be partially patent to small molecules for at least 6 months after the surgery. Whether increased passage of carbidopa into CSF and perhaps the transplant is of clinical significance has yet to be determined. Median CSF levodopa did not increase after surgery, probably because a limited defect in the BBB would be likely to be overshadowed by the effects of facilitated transport. CT scans performed following intravenous iothalamate meglumine contrast failed to reveal enhancement (dye leakage) near the transplantation site; however, artifact from the metal surgical clips used in the Madrazo procedure prevented good visualization of the area.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: J E
authors.initials: JE
authors.lastname: Ahlskog
authors.forename: G M
authors.initials: GM
authors.lastname: Tyce
authors.forename: P J
authors.initials: PJ
authors.lastname: Kelly
authors.forename: J A
authors.initials: JA
authors.lastname: van Heerden
authors.forename: S L
authors.initials: SL
authors.lastname: Stoddard
authors.forename: S W
authors.initials: SW
authors.lastname: Carmichael
mesh_terms: D000313:Adrenal Medulla / Q000637:transplantation*; D000328:Adult; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging; D002199:Capillary Permeability; D002230:Carbidopa / Q000097:blood / Q000134:cerebrospinal fluid; D002421:Caudate Nucleus / Q000503:physiopathology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000628:therapy; D012709:Serum Albumin / Q000032:analysis / Q000134:cerebrospinal fluid; D014057:Tomography, X-Ray Computed
chemical_list: D007074:Immunoglobulin G; D012709:Serum Albumin; D002230:Carbidopa