Central Nervous System Compartment Research Articles

The biodisposition of MPP+ in mouse brain.

These studies assessed the role of biotransformation in the rapid elimination of MPP+ from the central nervous system (CNS) compartment of mice. Mice were given either MPP+ via the intracerebroventricular (i.c.v.) route, or MPTP intraperitoneally. The elimination of MPP+ from the brain over 10 h was similar in both groups and followed exponential kinetics. Using liquid scintillation counting, high-pressure liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS) analysis, no compounds other than MPP+ were detected in brain 2-10 h after the i.c.v. administration of radiolabelled [14C/3H]MPP+. MPP+ was also unchanged after incubation with brain homogenates. These data indicate that MPP+ is not removed from the CNS compartment via biotransformation. Because of its positive charge and kinetics of elimination, the possibility of an active transport system is suggested.

Decrease of suppressor inducer (cd4+ 2h4+) t cells in multiple sclerosis cerebrospinal fluid

T-lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis are predominantly CD4+ (inducer) as opposed to CD8+ (suppressor/cytotoxic) T cells. The CD4+ lymphocytes can be subdivided into populations that express high densities of the CDw29 (4B4) determinant and have helper inducer function or express high densities of CD45R (2H4) determinant and have suppressor inducer function. In the present study, we characterized the nature of these CD4+ T cells in the cerebrospinal fluid of patients with multiple sclerosis by performing flow cytometric analysis on paired samples of blood and cerebrospinal fluid. There were significantly lower percentages of CD4+2H4+ T cells in the cerebrospinal fluid than in the peripheral blood (p = 0.001, paired t test). In contrast, there were increased percentages of helper inducer (CD4+4B4+) T cells in the cerebrospinal fluid (p = 0.001, paired t test), compared with the peripheral blood. Analysis of subjects with other inflammatory disorders of the central nervous system did not show significant decreases in CD4+2H4+ T cells in cerebrospinal fluid, though in some, decreases were also observed. These results indicate that the CD4+ T cells in the cerebrospinal fluid of patients with multiple sclerosis are predominantly helper inducer, as opposed to suppressor inducer T cells, and that the relative decrease of suppressor inducer cells in the peripheral blood of multiple sclerosis patients is not due to their migration to the cerebrospinal fluid. Furthermore, the increased numbers of helper inducer cells in the cerebrospinal fluid may contribute to local autoimmune processes in the central nervous system compartment of multiple sclerosis patients.

Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites.

Endothelial cells of human capillary blood vessels at the blood-brain and other blood-tissue barrier sites express P-glycoprotein as detected by mouse monoclonal antibodies against the human multidrug-resistance gene product. This pattern of endothelial cell expression may indicate a physiological role for P-glycoprotein in regulating the entry of certain molecules into the central nervous system and other anatomic compartments, such as the testes. These tissues, which limit the access of systemic drugs, are known pharmacologic sanctuaries for metastatic cancer. P-glycoprotein expression in capillary endothelium of brain and testes and not other tissues (i.e., kidney and placenta) may in part explain this phenomenon and could have important implications in cancer chemotherapy.

Chapter 29 Mammalian root-spinal cord regeneration

In adult mammals, it has been shown with modern morphological and histochemical techniques that regrowing nerve fibres in the dorsal root do not enter the spinal cord. This chapter describes the laboratory experiments on nerve fibre regeneration after dorsal root lesion and ventral root avulsion and medullar implantation. Experiments on dorsal root to spinal cord regrowth in the adult animals show that there is no difference in the regenerative capacity among neurons of different morphological, or neurochemical characteristics. The chapter suggests that regrowth of axons through the transition zone between the peripheral nervous system (PNS) and central nervous system (CNS) compartments at the root-spinal cord junction occurs after dorsal root severance in the immature animal and after ventral root avulsion injury and subsequent restoration of spinal cord-ventral root continuity. These findings appear to be encouraging examples of PNS-CNS neuronal regeneration. After an incomplete lesion, compensatory mechanisms like collateral sprouting from uninjured neurons, or neuronal neogenesis in the immature nervous system might influence the outcome of experiments and be misinterpreted as regeneration. Studies on root-spinal cord regeneration are therefore of great neurobiological and clinical importance.

Endorphins and exercise in females

Currently available measurements of beta-endorphin and beta-lipotropin in exercising women are in excellent agreement and indicate a 2-3 fold increase over basal levels. Possible effects of exercise upon the transfer of endorphins from the peripheral circulation to the brain are examined, and evidence is presented that suggests the occurrence of a concomitant exercise-related increase of endorphins in both humoral and central nervous system compartments. Steady-state measurements of circulating luteinizing hormone and follicle-stimulating hormone levels in oligo-amenorrheic athletes, on the other hand, do not agree. It is felt that the lack of consensus may be attributable partly to technical inadequacies and partly to lack of awareness of the need for frequent sampling. The bulk of the findings suggest a tendency for luteinizing hormone levels to be low and follicle-stimulating hormone levels to be normal or low, a pattern compatible with repeated activation of the CRH-ACTH-POMC system as a result of exercise.

The role of mast cells in virus-induced inflammation in the murine central nervous system

The mononuclear inflammatory response to Sindbis virus infection of the central nervous system is analogous to the cutaneous delayed-type hypersensitivity reaction. It is dependent on sensitized T cells for initiation, but many of the cells present are nonsensitized bone marrow-derived cells. Tissue mast cells have been shown to be important for the development of the delayed-type hypersensitivity reaction in the skin where capillary endothelial cells are joined by tight junctions. To determine whether mast cells are also important for the development of an immune-mediated inflammatory response across the endothelial tight junctions of the blood-brain barrier, the development of mononuclear inflammation in the central nervous system of reserpine-treated mice and mast cell-deficient mice (WBB6F 1-W/W v) was studied after infection with Sindbis virus. Three central nervous system compartments, the cerebrospinal fluid, the meninges, and the brain parenchyma, were evaluated for inflammation by counting the number of cells present, by grading the histopathologic lesions, and by labeling infiltrating cells with 125IUDR. By all parameters inflammation was reduced when mice were treated with reserpine or were deficient in mast cells. Antigen-specific humoral and cellular immune responses were depressed and virus clearance delayed in reserpine-treated mice, but not in mast cell deficient mice. It is concluded that the vasoactive amines released by mast cells in the central nervous system play a facilitating role in the development of the inflammatory response to Sindbis virus.

Clonal organization of the central nervous system of the frog. III. Clones stemming from individual blastomeres of the 128-, 256-, and 512- cell stages

Horseradish peroxidase injected into individual blastomeres of 128-, 256-, and 512-cell embyros of Xenopus laevis was identified in cells of the central nervous system (CNS) at early to middle larval stages. Labeled cells were dispersed, mingled with unlabeled cells. Four boundaries in the CNS could be defined by the behavior of clones of labeled cells: in the transverse plane at the level of the isthmus; in the horizontal plane between dorsal and ventral regions extending the entire length of the CNS; in the dorsal midline extending the entire length; and in the ventral midline of rhombencephalon and spinal cord but absent more rostrally. Cells injected with HRP at the 512-cell stage produced clones that, with rare exceptions, did not cross any boundary, whereas labeled clones initiated at earlier stages frequently crossed boundaries. Axons and dendrites were not restricted by these boundaries. These boundaries subdivided the CNS into seven compartments, each of which was occupied exclusively by the descendants of a group of 14 to 26 blastomeres in the 512-cell embryo. These groups of blastomeres formed a bilaterally symmetrical pattern composed of a single anterior median group straddling the dorsal midline near the animal pole and three groups on each side. Because cells mingled in each compartment but not across compartmental boundaries, there was a one-to-one relationship between individual blastomeres and CNS compartments but one-many and many-one relationships between individual blastomeres and neuroanatomical subdivisions smaller than a compartment. There was no constant relationship between phenotypes of nerve cells and their ancestry from individual blastomeres of the 512-cell or earlier stages.

Intrathecal synthesis of immunoglobulin light chains in a child with late-onset agammaglobulinemia

In a 4-year-old child with late-onset agammaglobulinemia and neurologic disturbances of unknown etiology, immunoglobulin light chains were detected in the cerebrospinal fluid but not in the serum by immunofixation after isoelectric focussing. This finding supports the hypothesis that the central nervous system compartment of the immune system is at least partly capable of autonomous Ig synthesis.