Browsing by Author "Segal, M.B. (7201773258)"

Blood-brain barrier permeability to homologous serum125I-IgG and to D-[3H]mannitol was studied by means of the brain vascular perfusion method in guinea pigs with experimental allergic encephalomyelitis (EAE). EAE was induced with homologous myelin basic protein (MBP) after pretreatment with foreign protein and muramyl dipeptide (MDP). The results suggest a significant comparable increase in IgG blood-to-brain clearance in the parietal cortex, hippocampus, and caudate nucleus, during vascular perfusion of the brains of animals, after 7 and 20 days of EAE. On the other hand, unidirectional transfer of mannitol in the same period of EAE was markedly augmented only in the hippocampus, but no significant changes in the parietal cortex or caudate nucleus were observed. Cerebrospinal fluid (CSF)/serum ratios for IgG and albumin were both significantly increased, suggesting an increase in blood-CSF barrier permeability, but more for albumin than for IgG. The results were confirmed by immunohistochemical determination of the IgG deposits in the brains of EAE animals, during vascular perfusion with unlabeled homologous IgG. An important role of the blood-brain barrier for the central nervous system immunoglobulin homeostasis during EAE is suggested. © 1989 Plenum Publishing Corporation.

Blood-brain barrier permeability to homologous serum125I-IgG and to D-[3H]mannitol was studied by means of the brain vascular perfusion method in guinea pigs with experimental allergic encephalomyelitis (EAE). EAE was induced with homologous myelin basic protein (MBP) after pretreatment with foreign protein and muramyl dipeptide (MDP). The results suggest a significant comparable increase in IgG blood-to-brain clearance in the parietal cortex, hippocampus, and caudate nucleus, during vascular perfusion of the brains of animals, after 7 and 20 days of EAE. On the other hand, unidirectional transfer of mannitol in the same period of EAE was markedly augmented only in the hippocampus, but no significant changes in the parietal cortex or caudate nucleus were observed. Cerebrospinal fluid (CSF)/serum ratios for IgG and albumin were both significantly increased, suggesting an increase in blood-CSF barrier permeability, but more for albumin than for IgG. The results were confirmed by immunohistochemical determination of the IgG deposits in the brains of EAE animals, during vascular perfusion with unlabeled homologous IgG. An important role of the blood-brain barrier for the central nervous system immunoglobulin homeostasis during EAE is suggested. © 1989 Plenum Publishing Corporation.

Effects of sensory-motor cortical lesions on the function of the blood-brain barrier in distant brain areas are poorly understood. Therefore a brain vascular perfusion method has been used to measure simultaneously the kinetics of entry of two inert polar molecules, D[14C]mannitol (MW 180) and [3H]polyethylene glycol (PEG; MW 4000), into the parietal cortex, hippocampus, and caudate nucleus in guinea pigs with ipsilateral and contralateral sensorymotor cortical lesions. The graphically determined cerebral capillary unidirectional constant, Kin, indicated a marked increase in blood-to-brain transport of both molecules in all regions studied, the changes being significantly higher after contralateral lesion. The mannitol/PEG cerebrovascular permeability constant ratio, Pman/PPEG, suggested the opening up of channels that permit a flow of fluid carrying substances either with respect to (2 days after ipsilateral lesion) or irrespective of their molecular size, depending on the time after lesion. Amphetamine treatment in the guinea pigs with sensory-motor lesions induced more pronounced blood-brain barrier permeability changes for both molecules in distant brain areas. © 1989 Plenum Publishing Corporation.

Effects of sensory-motor cortical lesions on the function of the blood-brain barrier in distant brain areas are poorly understood. Therefore a brain vascular perfusion method has been used to measure simultaneously the kinetics of entry of two inert polar molecules, D[14C]mannitol (MW 180) and [3H]polyethylene glycol (PEG; MW 4000), into the parietal cortex, hippocampus, and caudate nucleus in guinea pigs with ipsilateral and contralateral sensorymotor cortical lesions. The graphically determined cerebral capillary unidirectional constant, Kin, indicated a marked increase in blood-to-brain transport of both molecules in all regions studied, the changes being significantly higher after contralateral lesion. The mannitol/PEG cerebrovascular permeability constant ratio, Pman/PPEG, suggested the opening up of channels that permit a flow of fluid carrying substances either with respect to (2 days after ipsilateral lesion) or irrespective of their molecular size, depending on the time after lesion. Amphetamine treatment in the guinea pigs with sensory-motor lesions induced more pronounced blood-brain barrier permeability changes for both molecules in distant brain areas. © 1989 Plenum Publishing Corporation.

Tiazofurin (TZF- beta-D-ribofuranosyl thiazole-4-carboxamide, NSC- 286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [ 3 H]-tiazofurin was determined in relation to the recovery of [ 14 C]- mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 ± 0.84% and was shown to be both carrier- mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 ± 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a K(m) 7.71 ± 1.42 μM, a V(max) of 1.30 ± 0.05 μM/min/g and a negligible constant of a free diffusion (K(2)) which suggests that the CP/CSF route may act as an alternative pathway into the brain. (C) 2000 Prous Science.

Tiazofurin (TZF- beta-D-ribofuranosyl thiazole-4-carboxamide, NSC- 286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [ 3 H]-tiazofurin was determined in relation to the recovery of [ 14 C]- mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 ± 0.84% and was shown to be both carrier- mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 ± 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a K(m) 7.71 ± 1.42 μM, a V(max) of 1.30 ± 0.05 μM/min/g and a negligible constant of a free diffusion (K(2)) which suggests that the CP/CSF route may act as an alternative pathway into the brain. (C) 2000 Prous Science.