Abstract
The microvessels of the pia mater lack an investment with astrocyte processes but nonetheless have a high transendothelial electrical resistance which has caused them to be regarded as part of the blood-brain barrier. This high resistance is known to be acquired in the perinatal period. The aim of our study was to relate the known physiological changes with differentiation of the endothelial paracellular clefts and especially of their tight junctions which provide the basis for the high transendothelial resistance of blood-brain barrier vessels. Tight junctions of endothelial cell paracellular clefts in pial microvessels were examined by transmission electron microscopy using goniometric tilting to reveal and measure membrane separations at tight junctions in fetal, postnatal and adult rats. These tight junctional membrane separations narrowed over the period (E16:6.3 nm, D1:6.4 nm, D7:5.4 nm) and differentiated into two groups by the adult stage: one with a membrane separation of 2.8 nm and the staining characteristics of non-brain endothelial junctions, and the other with no detectable membrane separation and the staining characteristic of blood-brain barrier endothelial junctions. This patchy and incomplete differentiation of pial tight junctions into a blood-brain barrier-like form could result either from non-uniform exposure to inductive signals or to local variation in responsiveness to such agents. Although these changes in junction organization may be related to the known increase in pial transendothelial resistance in the perinatal period, we have not yet identified any sharply defined structural change which coincides with this physiological event.
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Abbott, N. J., Revest, P. A. & Romero, I. A. (1992) Astrocyte-endothelial interaction: physiology and pathology. Neuropathology and Applied Neurobiology 18, 424–33.
Abrunhosa, R. (1972) Microperfusion fixation of embryos for ultrastructural studies. Journal of Ultrastructure Research 41, 176–80.
Brightman, M. W. & Reese, T. S. (1969) Junctions between intimately apposed cell membranes in the vertebrate brain. Journal of Cell Biology 40, 648–77.
Butt, A. M., Jones, H. C. & Abbott, N. J. (1990) Electrical resistance across the blood-brain barrier in anaesthetised rats: a developmental study. Journal of Physiology 429, 47–62.
Bundgaard, M. (1984) The three-dimensional organisation of tight junctions in a capillary endothelium revealed by serial-section electron microscopy. Journal of Ultrastructure Research 88, 1–17.
Bundgaard, M. & FrØkjaer-Jensen, J. (1982) Functional aspects of the ultrastructure of terminal blood vessels: a quantitative study on consecutive segments of the frog mesenteric microvasculature. Microvascular Research 23, 1–30.
Cassella, J. P., Lawrenson, J. G. & Firth, J. A. (1996) Ontogeny of four blood-brain barrier markers: an immunocytochemical comparison of pial and cerebral cortical microvessels. Journal of Anatomy 189, 407–15.
Cassella, J. P., Lawrenson, J. G., Lawrence, L. & Firth, J. A. (1997) Differential expression of an endothelial barrier antigen between the pial and cortical microvessels of the rat. Brain Research 744, 335–8.
Dermietzel, R. & Krause, D. (1991) Molecular anatomy of the blood-brain barrier as defined by immunocytochemistry. International Review of Cytology 127, 57–109.
Firth, J. A., Bauman, K. F. & Sibley, C. P. (1983) The intercellular junctions of guinea-pig placental capillaries: a possible structural basis for endothelial solute permeability. Journal of Ultrastructure Research 85,45–57.
Hurwitz, A. A., Berman, J. W., Rashbaum, W. K. & Lyman, W. D. (1993) Human fetal astrocytes induce the expression of blood-brain specific proteins by autologous endothelial cells. Brain Research 625, 238–43.
Janzer, R. C. & Raff, M. C. (1987) Astrocytes induce blood-brain properties in endothelial cells. Nature 325, 253–7.
Keep, R. F., Xiang, J., Ennis, S. R., Beer, M. E. & Betz, A. L. (1993) Brain volume regulation during development: the role of blood-brain barrier potassium transport. Advances in Experimental Medicine and Biology 331, 65–9.
Keep, R. F., Ennis, S. R., Beer, M. E. & Betz, A. L. (1995) Developmental change in blood-brain barrier potassium permeability in the rat: relation to brain growth. Journal of Physiology 488, 439–48.
Lawrenson, J. G., Ghabriel, M. N., Reid, A. R., Gajree, T. N. & Allt, G. (1995a) Distribution of a putative endothelial barrier antigen in the ocular and orbital tissues of the rat. British Journal of Ophthalmology 79, 462–6.
Lawrenson, J. G., Ghabriel, M. N., Reid, A. R., Gajree, T. N. & Allt, G. (1995b) Differential expression of an endothelial barrier antigen between the CNS and PNS. Journal of Anatomy 186, 217–21.
Lobrinus, J. A., Juillerat-Jenneret, L., Darekar, P., Schlosshauer, B. & Janzer, R. C. (1992) Induction of the blood-brain barrier specific HT7 and neurothelin epitopes in endothelial cells of the chick chorioallantoic vessels by a soluble factor derived from astrocytes. Developmental Brain Research 70, 207–11.
MØllgard, K. & Saunders, N. (1975) Complex tight junctions of epithelial and of endothelial cells in early foetal brain. Journal of Neurocytology 4, 453–68.
Neuhaus, J., Risau, W. & Wolburg, H. (1991) Induction of blood-brain barrier characteristics in bovine brain endothelial cells by rat astroglial cells in transfilter coculture. Annals of the New York Academy of Sciences 633, 578–80.
Olsson, Y., Klatzo, I., Sourander, P. & Steinwall, O. (1968) Blood-brain barrier to albumin in embryonic, newborn and adult rats. Acta Neuropathologica 10, 117–22.
Raub, T. J., Kuentzel, S. L. & Sawada, G. A. (1992) Permeability of bovine brain microvessel endothelial cells in vitro: barrier tightening by a factor released from astroglioma cells. Experimental Cell Research 199, 330–40.
REESE, T. S. & KARNOVSKY, M. J. (1967) Fine structural localisation of a blood-brain barrier to exogenous peroxidase. Journal of Cell Biology 34, 207–17.
Rhodin, J. A. G. (1968) Ultrastructure of mammalian venous capillaries, venules and small collecting veins. Journal of Ultrastructure Research 25, 452–500.
Risau, W., Hallmann, R., Albrecht, U. & Henke-Fahle, S. (1986) Brain induces the expression of an early cell surface marker for blood-brain barrier specific endothelium. EMBO Journal 5, 3179–83.
Rowan, R. A. & Maxwell, D. S. (1981) Patterns of vascular sprouting in the postnatal development of the cerebral cortex of the rat. American Journal of Anatomy 160, 247–55.
Rubin, L. L., Hall, D. E., Porter, S., Barbu, K., Cannon, C., Horner, H. C., Janatpour, M., Liaw, C. W., Manning, K., Morales, J., Tanner, L. I., Tomasselli, K. J. & Bard, F. (1992) A cell culture model of the blood-brain barrier. Journal of Cell Biology 115, 1725–35.
Schulze, C. & Firth, J. A. (1992a) The interendothelial junction in myocardial capillaries: evidence for the existence of regularly spaced, cleft-spanning structures. Journal of Cell Science 101, 647–55.
Schulze, C. & Firth, J. A. (1992b) The interendothelial junctions during blood-brain barrier development in the rat: morphological changes at the level of individual tight junctional contacts. Developmental Brain Research 69, 85–95.
Sessa, G. & Perez, M. M. (1975) Biochemical changes in rat brain associated with the development of the blood-brain barrier. Journal of Neurochemistry 25, 779–82.
Simionescu, N. & SIMIONESCU, M. (1976) Galloylglucoses of low molecular weight as mordant in electron microscopy. I. Procedure and evidence for mordanting effect. Journal of Cell Biology 70, 608–21.
Sternberger, N. H. & STERNBERGER, L. A. (1987) Blood-brain barrier protein recognised by a monoclonal antibody. Proceedings of the National Academy of Sciences USA 84, 8169–73.
Sternberger, N. H. & Sternberger, L. A., Kies, M. W. & Shear, C. R. (1989) Cell surface endothelial proteins altered in experimental allergic encephalomyelitis. Journal of Neuroimmunology 21, 241–8.
Weibel, E. R. (1969) Stereological principles for morphometry in electron microscopic cytology. International Review of Cytology 26, 235–302.
Wolburg, H., Neuhaus, J., Kniesel, U., Krauss, B., Schmid, E.-M., Öcalan, M., Farrell, C. & RISAU, W. (1994) Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes. Journal of Cell Science 107, 1347–57.
Xu, J. & Ling, E.-A. (1994) Studies of the ultrastructure and permeability of the blood-brain barrier in the developing corpus callosum in postnatal rat brain using electron dense tracers. Journal of Anatomy 184, 227–37.
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Cassella, J.P., Lawrenson, J.G. & Firth, J.A. Development of Endothelial Paracellular Clefts and their Tight Junctions in the Pial Microvessels of the Rat. J Neurocytol 26, 567–575 (1997). https://doi.org/10.1023/A:1015438624949
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DOI: https://doi.org/10.1023/A:1015438624949