Summary
An ultracytochemical investigation was performed to study the origin of pinocytic vesicles and canalicular structures within endothelial cells (EC) of the injured mammalian blood-brain barrier (BBB). To accomplish this goal, two electron-dense tracers, native ferritin (NF) and horseradish peroxidase (HRP), were used in conjunction with the detection of alkaline phosphatase (AP) activity, a known marker of EC plasmalemma of brain micro-blood vessels.
Brain ECs from (1) mice subjected to crude leptomeningeal damage for 1, 2, or 3 days and (2) cats subjected to cold lesion injury for 1, 4, or 24h were evaluated for tracer transport and AP activity. Fine structural analysis of leaking segments of micro-blood vessels from damaged cerebral cortex or basal ganglia demonstrated pinocytic vesicles, deep invaginations of the luminal plasmalemma and elongated, tubular profiles, all containing tracer.
Because we observed in ECs from both experimental models of brain injury a positive reaction for AP activity in the luminal plasmalemma, in its deep invaginations, in deliminating membranes of pinocytic vesicles, and in tubulo-canalicular structures, we conclude that all types of transport structures derive from the same 100Å thick exoplasmic plasmalemmal membranes. Further, besides the pinocytic vesicular transport system (PTS), the canalicular transport system (CTS) appears to serve as an additional important mechanism for macromolecular transport across the damaged mammalian BBB.
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References
Beggs JL, Waggener JD (1976) Transendothelial vesicular transport of protein following compression injury to the spinal cord. Lab Invest 34:428–439
Brightman MW, Hori M, Rapoport SI, Reese TS, Westergaard E (1973) Osmotic opening of tight junctions in cerebral endothelium. J Comp Neurol 152:317–326
De Bruyn PPH, Michelson S, Becker RP (1975) Endocytosis, transfer tubules, and lysosomal activity in myeloid sinusoidal endothelium. J Ultrastruct Res 53:133–151
De Bruyn PPH, Michelson S, Becker RP (1977) Phosphotungstic acid as a marker for the endocytic-lysosomal system (vacuolar apparatus) including transfer tubules of the lining cells of the sinusoids in bone marrow and liver. J Ultrastruct Res 58:87–95
Garcia JH, Klatzo I, Archer T, Lossinsky AS (1981) Arterial air embolism: Structuraleffects on the gerbil brain. Stroke 12:414–421
Houthoff HJ, Go KG (1980) Endogenous versus exogenous protein tracer passage in blood-brain barrier damage. In: Cervos-Navarro J, Ferszt R (eds) Brain edema, vol 28, Raven Press, New York, pp 75–81
Houthoff HJ, Go KG, Gerrits PO (1982) The mechanisms of bloodbrain barrier impairment by hyperosmolar perfusion. An electron cytochemical study comparing exogenous HRP and endogenous antibody to HRP as tracers. Acta Neuropathol (Berl) 56:99–112
Klatzo I, Chui E, Fujiwara K, Spatz M (1980) Resolution of vasogenic brain edema. In: Cervos-Navarro J, Ferszt R (eds) Brain edema, vol 28. Raven Press, New York, pp 359–373
Lossinsky AS, Garcia JH, Iwanowski L, Lightfoote WE Jr (1979) New ultrastructural evidence for a protein transport system in endothelial cells of gerbil brains. Acta Neuropathol (Berl) 47:105–110
Lossinsky AS, Vorbrodt AW, Wisniewski HM, Iwanowski L (1981a) Ultracytochemical evidence for endothelial channel-lysosome connections in mouse brain following blood-brain barrier changes. Acta Neuropathol (Berl) 53:197–202
Lossinsky AS, Vorbrodt AW, Wisniewski HM, Moretz RC (1981b) A simple screening procedure for evaluating central nervous system tissue sections showing structural and cytochemical alterations of the blood-brain barrier. Stain Technol 56:279–282
Mayhara H, Hirano H, Saito T, Ogawa K (1967) The new lead citrate method for the ultracytochemical demonstration of non-specific alkaline phosphatase. Histochemie 1:88–96
Nag S, Robertson DM, Dinsdale HB (1977) Cerebral cortical changes in acute experimental hypertension. An ultrastructural study. Lab Invest 36:150–161
Nichols BA (1982) Uptake and digestion of horseradish peroxidase in rabbit alveolar macrophages. Formation of a pathway connecting lysosomes to the cell surface. Lab Invest 47:235–246
Peters A, Palay SL, Webster H DeF (1976) The fine structure of the nervous system: The neurons and supporting cells. Saunders, Philadelphia, pp 295–305
Rapoport SI, Hori M, Klatzo I (1972) Reversible osmotic opening of the blood-brain barrier. Science 173:1026–1028
Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:207–217
Simionescu N, Simionescu M, Palade GE (1975) Permeability of muscle capillaries to small heme-peptides. Evidence for the existence of patent transendothelial channels. J Cell Biol 64:586–607
Simionescu N, Simionescu M, Palade GE (1978) Structural basis of permeability in sequential segments of the microvasculature of the diaphragm. II. Pathways followed by microperoxidase across the endothelium. Microvasc Res 15:17–36
Spurr AR (1969) A low-viscosity resin embedding medium for electron microscopy. J Ultrastruct Res 26:31
Trump BF, McDowell EM, Astila AU (1980) Cellular reaction to injury. In: Hill RB Jr, LaVia MF (eds) Principles of pathobiology. 3rd edn. Oxford University Press, New York, pp 20–111
Vorbrodt AW, Lossinsky AS, Wisniewski HM, Moretz RC, Iwanowski L (1981a) Ultrastructural cytochemical studies of cerebral microvasculature in scrapie infected mice. Acta Neuropathol (Berl) 53:203–211
Vorbrodt AW, Lassmann H, Wisniewski HM, Lossinsky AS (1981b) Ultracytochemical studies of the blood-meningeal barrier (BMB) in rat spinal cord. Acta Neuropathol (Berl) 55:113–123
Vorbrodt AW, Lossinsky AS, Wisniewski HM (1983) Enzyme cytochemistry of blood-brain barrier (BBB) disturbances. Acta Neuropathol (Berl) [Suppl] VIII:43–57
Westergaard E (1975) Enhanced vesicular transport of exogenous peroxidase across cerebral vessels, induced by serotonin. Acta Neuropathol (Berl) 32:27–42
Westergaard E, Go G, Klatzo I, Spatz M (1976) Increased permeability of cerebral vessels to horseradish peroxidase induced by ischemia in mongolian gerbits. Acta Neuropathol (Berl) 35:307–325
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Supported in part by a grant from the NINCDS No. NS18079-01
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Lossinsky, A.S., Vorbrodt, A.W. & Wisniewski, H.M. Ultracytochemical studies of vesicular and canalicular transport structures in the injured mammalian blood-brain barrier. Acta Neuropathol 61, 239–245 (1983). https://doi.org/10.1007/BF00691992
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DOI: https://doi.org/10.1007/BF00691992