Summary
The present investigation focused on the structural events occurring in endothelial cells lining the lumina of brain microvessels in rats subjected to a single intracarotid injection of hypertonic 1.8m l (+) arabinose solution with or without intravenous injection of horseradish peroxidase. Blood vessels from cerebral cortex and thalamus were evaluated by transmission and scanning electron microscopy. After short-term exposure (10–12 min) there was widespread flooding of peroxidase into the brain neuropil of the ipsilateral hemisphere. Peroxidase tracer was frequently observed within vesiculo-tubular profiles, and occasionally within widened interendothelial junctional clefts. Partially fragmented, necrotic endothelial cells appeared to be in the process of desquamation. Individual endothelial cells appeared to be shrunken with widened interendothelial spaces. Some healthy endothelial cells appeared to be involved in repair processes, manifested by the extension of thin cellular processes towards the area of vessel injury. Other pathological alterations included a conspicuous increase in the number of endothelial cell microvilli, large crater-like invaginations of the endothelial plasma membranes and muscular blood vessels in the process of spasm. We also observed a platelet reaction with or without endothelial cell necrosis and attached microthrombi in some arterial segments.
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Balin, B. J., Broadwell, R. D. &Salcman, M. (1987) Tubular profiles do not form transendothelial channels through the blood-brain barrier.Journal of Neurocytology 16, 721–35.
Beggs, J L. &Waggener, J. D. (1976) Transendothelial vesicular transport of protein following compression injury to the spinal cord.Laboratory Investigation 34, 428–39.
Brightman, M. W. (1989) The anatomic basis of the blood-brain barrier. InImplications of the blood-brain barrier and its manipulation (edited byNeuwelt, E. A.) pp. 53–83., New York: Plenum Publishing Corp.
Brightman, M. W., Hori, M., Rapoport, S. I., Reese, T. S. &Westergaard, E. (1973) Osmotic opening of tight junctions in cerebral endothelium.Journal of Comparative Neurology 152, 317–25.
Broadwell, R. D. (1989) Transcytosis of macromolecules through the blood-brain barrier: a cell biological perspective and critical appraisal.Acta Neuropathologica 79, 117–28.
Cannella, B., Cross, A. H. &Raine, C. S. (1991) Adhesion-related molecules in the central nervous system. Upregulation correlates with inflammatory cell influx during relapsing experimental autoimmune encephalomyelitis.Laboratory Investigation 65, 23–31.
Cross, A. E. &Raine, C. S. (1991) Central nervous system endothelial cell-polymorphonuclear cell interactions during autoimmune demyelination.American Journal of Pathology 139, 1401–9.
Farrell, C. L. &Shivers, R. R. (1984) Capillary junctions of the rat are not affected by osmotic opening of the blood-brain barrier.Acta Neuropathologica 63, 179–89.
Garcia, J. H., Liu, K. F., Yoshida, Y., Lian, J., Chen, S. &Del Zoppo, G. J. (1994) Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat).American Journal of Pathology 144, 188–99.
Hiesiger, E. M., Voorhies, R. M., Basler, M. A., Lipschutz, B. S., Posner, J. B. &Shapiro, W. R. (1986) Opening of the blood-brain and blood-tumor barriers in experimental rat brain tumors: the effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow.Annals of Neurology 19, 50–9.
Houthoff, H. J. &Go, K. G. (1980) Endogenous versus exogenous protein tracer passage in blood-brain barrier damage. InAdvances in Neurology (edited byCervos-Navarro, J. &Ferszt, R.) pp. 75–81. New York: Raven Press.
Houthoff, H. J., Go, K. G. &Gerrits, P. O. (1982) The mechanisms of blood-brain barrier impairment by hyperosmolar perfusion. An electron cytochemical study comparing exogenous HRP and endogenous antibody to HRP as tracers.Acta Neuropathologica 56, 99–112.
Hughes, J. T. (1987) Endothelial changes in baboon cerebral arteries after experimental arterial spasm: a study using scanning electron microscopy. InStroke and Microcirculation (edited byCervos-Navarro, J. &Ferszt, R.) pp. 487–94. New York: Raven Press.
Kumar, K., White, B., Krause, G., Garritano, A. M. &Koestner, A. (1987) Cerebral endothelium microvilli following global brain ischemia in dogs.Brain Research 421, 309–14.
Lossinsky, A. S. &Wisniewski, H. M. (1986) A comparative ultrastructural study of endothelial cell tubular structures from injured mouse blood-brain barrier and normal hepatic sinusoids demonstrated after perfusion fixation with osmium tetroxide.Microvascular Research 31, 333–4.
Lossinsky, A. S., Garcia, J. H., Iwanowski, L. &Lightfoote, W. E., Jr. (1979) New ultrastructural evidence for a protein transport system in endothelial cells of gerbil brains.Acta Neuropathologica 47, 105–10.
Lossinsky, A. S., Song, M. J. &Wisniewski, H. M. (1989) High voltage electron microscopic studies of endothelial cell tubular structures in the mouse blood-brain barrier following brain trauma.Acta Neuropathologica 77, 480–8.
Lossinsky, A. S., Pluta, R., Song, M. J., Badmajew, V., Moretz, R. C. &Wisniewski, H. M. (1991) Mechanisms of inflammatory cell attachment in chronic relapsing experimental allergic encephalomyelitis: a scanning and high-voltage electron microscopic study of the injured mouse blood-brain barrier.Microvascular Research 41, 299–310.
Macdonald, R. L., Weir, B. K. A., Chen, M. H. &Grace, M. G. A. (1991) Scanning electron microscopy of normal and vasospastic monkey cerebrovascular smooth muscle cells.Neurosurgery 29, 544–50.
Nag, S., Robertson, D. M. &Dinsdale, H. B. (1977) Cerebral cortical changes in acute experimental hypertension. An ultrastructural study.Laboratory Investigation 36, 150–61.
Neuwelt, E. A., Goldman, D., Dahlborg, S. A., Crossen, J., Ramsey, F., Roman-Goldstein, S., Braziel, R. &Dana, B. (1991) Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function.Journal Clinical Oncology 9, 1580–90.
Oldendorf, W. H. &Brown, W. J. (1975) Greater number of capillary endothelial cell mitochondria in brain than in muscle.Proceedings for the Society of Experimental Biology and Medicine 149, 736–8.
Oldendorf, W. H., Cornford, M. E. &Brown, W. J. (1977) The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat.Annals of Neurology 1, 409–17.
Peters, A., Palay, S. L. &Webster, H. de F. (1976) Blood vessels. InThe Fine Structure of the Nervous System: The Neurons and Supporting Cells (edited byPeters, A., Palay, S. L. &Webster, H. de F.) pp. 295–305. Philadelphia: W. B. Saunders Co.
Pluta, R., Lossinsky, A. S., Mossakowski, M. J., Faso, L. &Wisniewski, H. M. (1991) Reassessment of a new model of complete cerebral ischemia in rats. Methods of induction of clinical death, pathophysiology and cerebrovascular pathology.Acta Neuropathologica 83, 1–11.
Pluta, R., Lossinsky, A. S., Walski, M., Wisniewski, H. M. &Mossakowski, M. J. (1994) Platelet occlusion phenomenon after short- and long-term survival following complete cerebral ischemia in rats produced by cardiac arrest.Journal of Brain Research 35, 463–71.
Raine, C. S., Cannella, B., Duijvestljn, A. M. &Cross, A. H. (1990) Homing to central nervous system vasculature by antigen-specific lymphocytes. II. Lymphocyte/endothelial cell adhesion during the initial stages of autoimmune demyelination.Laboratory Investigation 63, 476–89.
Rapoport, S. I., Hori, M. &Klatzo, I. (1972) Testing of a hypothesis for osmotic opening of the blood-brain barrier.American Journal of Physiology 223, 323–31.
Reese, T. S. &Karnovsky, M. J. (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase.Journal of Cell Biology 34, 207–17.
Rosenblum, W. I. (1986) Biology of disease. Aspects of endothelial malfunction and function in cerebral microvessels.Laboratory Investigation 55, 252–8.
Shivers, R. R. (1979) The effect of hyperglycemia on brain capillary permeability in the lizard,Anolis carolinensis. A freeze-fracture analysis of blood-brain barrier pathology.Brain Research 170, 509–22.
Sholley, M. M., Gimbrone, M. A. &Cotran, R. S. (1977) Cellular migration and replication in endothelial regeneration.Laboratory Investigation 36, 18–25.
Simionescu, N., Simionescu, M. &Palade, G. E. (1975) Permeability of muscle capillaries to small heme-peptides. Evidence for the existence of patent transendothelial channels.Journal of Cell Biology 64, 586–607.
Trump, B. F., Mcdowell, E. M. &Arstila, A. U. (1980) Cellular reaction of injury. InPrinciples of Pathobiology (edited byHill, R. B. Jr &Lavia, M. F.) pp. 20–103. New York: Oxford University Press.
Vorbrodt, A. W. (1988) Ultrastructural cytochemistry of the blood-brain barrier.Progress in Histochemistry and Cytochemistry 18, 1–99.
Vorbrodt, A. W., Dobrogowska, D. H., Tarnawski, M. &Lossinsky, A. S. (1994) A quantitative immunocytochemical study of the osmotic opening of the blood-brain barrier to endogenous albumin.Journal of Neurocytology 23, 792–800.
Vorbrodt, A. W., Lossinsky, A. S., Dobrogowska, D. H. &Wisniewski, H. M. (1993) Cellular mechanisms of the blood-brain barrier (BBB) opening to albumin-gold complex.Histology Histopathology 8, 51–61.
Wisniewski, H. M. &Lossinsky, A. S. (1991) Structural and functional aspects of the interaction of inflammatory cells with the blood-brain barrier in experimental brain inflammation.Brain Pathology 1, 89–96.
Wisniewski, H. M., Pluta, R., Lossinsky, A. S. &Mossakowski, M. J. (1995) Ultrastructural studies of cerebral vascular spasm after cardiac arrest-produced global ischemia in rats.Acta Neuropathologica, in press.
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Lossinsky, A.S., Vorbrodt, A.W. & Wisniewski, H.M. Scanning and transmission electron microscopic studies of microvascular pathology in the osmotically impaired blood-brain barrier. J Neurocytol 24, 795–806 (1995). https://doi.org/10.1007/BF01191215
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DOI: https://doi.org/10.1007/BF01191215