Pathological Alterations in the Cerebral

Hirano, Atsushi; Becker, Norwin H.; Zimmerman, H. M.

doi:10.1001/archneur.1969.00480090088013

Cited by 62 publications

(1 citation statement)

References 10 publications

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“…Increased permeability of the BBB to HRP has also been induced by a stab wound (Hirano, Becker & Zimmerman, 1969, 1970, 3 M urea injection (Brightman, Hori, Rapoport, Reese & Westergaard, 1973), intoxication with methyl mercuric chloride (Ware, Chang & Burkholder, 1974) and radiation injury (Olsson, Klatzo & Carsten, 1975). Enhanced production of vesicles in endothelial cells can be induced by serotonin (Westergaard, 1975a;b) and histamine (Job, Rakonczay & Wollemann, 1975).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Permeability to Horseradish Peroxidase Across Cerebral Vessels in the Rat After Portocaval Anastomosis

Laursen

Westergaard

1977

Neuropathology Appl Neurobio

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Enhanced permeability to horseradish peroxidase across cerebral vessels in the rat after portocaval anastomosisThe blood-brain barrier to horseradish peroxidase (HRP) was examined in rats 10 or 30 days after establishing an end-to-side portocaval anastomosis. An increased number of vesicles containing HRP were seen in the endothelial cells of arterioles and to a lesser degree in the endothelial cells of venules and capillaries. Peroxidase was not found in the interendothelial space between tight junctions, which were everywhere intact. The basement membranes of vessels and the neuropil adjacent to these could contain the tracer. Astrocytic endfeet were swollen 10 days after the operation and contained only a few organelles. Thirty days after the operation reactive changes seemed to occur in astrocytes, indicated by less swelling and enhanced number of organelles. The cytoplasm of the astrocytes in some instances was evenly stained by reaction product. A similar staining was very occasionally observed in a few neuronal processes. It is concluded that an increased vesicular transport of HRP is inferred to have occurred across cerebral endothelium in animals after PCA and that the astrocytes may be especially sensitive to damage to the plasma membrane during liver shunt encephalopathy leading to intracellular uptake of substances from the extracellular space.

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Section: Discussionmentioning

confidence: 99%

Enhanced Permeability to Horseradish Peroxidase Across Cerebral Vessels in the Rat After Portocaval Anastomosis

Laursen

Westergaard

1977

Neuropathology Appl Neurobio

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Intracellular channels as a route for protein passage in the capillary endothelium of the shark brain

Hashimoto

1972

Am. J. Anat.

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Capillaries in the area postrema and other brain regions at the level of the obex were examined in Japanese sharks under the electron microscope with or without intravascular injection of horse-radish peroxidase and histochemical incubation. The postremal capillaries were characterized by a relatively wide perivascular space filled with connective tissue elements including fine fibrils about 100 A in diameter, and by endothelial fenestration; however, the space and fenestration were apparently less extensive than in rats and cats (Hashimoto, '66; Rivera-Pomar, '66; Hashimoto and Hama, '68). In other brain regions, the capillary endothelium showed peroxidase-filled intracellular channels that connected the luminal surface with the basement membrane soon after peroxidase injection. Many of the adjoining endothelial cells were linked by tight junctions. Perivascular astrocytic processes had long, tight contacts of about 125 A in overall thickness. Discussion was focused on a possible endothelial route for passage of $0-called barrier-free substances in the central nervous system of higher vertebrates.

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Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey

Balin

Broadwell

Salcman

et al. 1986

J of Comparative Neurology

320

163

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Pathways traversed by peripherally administered protein tracers for entry to the mammalian brain were investigated by light and electron microscopy. Native horseradish peroxidase (HRP) and wheat germ agglutinin (WGA) conjugated to peroxidase were administered intranasally, intravenously, or intraventricularly to mice; native HRP was delivered intranasally or intravenously to rats and squirrel monkeys. Unlike WGA-HRP, native HRP administered intranasally passed freely through intercellular junctions of the olfactory epithelia to reach the olfactory bulbs of the CNS extracellularly within 45-90 minutes in all species. The olfactory epithelium labeled with intravenously delivered HRP, which readily escaped vasculature supplying this epithelium. Blood-borne peroxidase also exited fenestrated vessels of the dura mater and circumventricular organs. This HRP in the mouse, but not in the other species, passed from the dura mater through patent intercellular junctions within the arachnoid mater; in time, peroxidase reaction product in the mouse brain was associated with the pial surface, the Virchow-Robin spaces of vessels penetrating the pial surface, perivascular clefts, and with phagocytic pericytes located on the abluminal surface of superficial and deep cerebral microvasculature. Blood-borne HRP was endocytosed avidly at the luminal face of the cerebral endothelium in all species. WGA-HRP and native HRP delivered intraventricularly to the mouse were not endocytosed appreciably at the abluminal surface of the endothelium; hence, the endocytosis of protein and internalization of cell surface membrane within the cerebral endothelium are vectorial. The low to non-existent endocytic activity and internalization of membrane from the abluminal endothelial surface suggests that vesicular transport through the cerebral endothelium from blood to brain and from brain to blood does not occur. The extracellular pathways through which probe molecules enter the mammalian brain offer potential routes of passage for blood-borne and air-borne toxic, carcinogenic, infectious, and neurotoxic agents and addictive drugs, and for the delivery of chemotherapeutic agents to combat CNS infections and deficiency states. Methodological considerations are discussed for the interpretation of data derived from application of peroxidase to study the blood-brain barrier.

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Pathological Alterations in the Cerebral

Cited by 62 publications

References 10 publications

Enhanced Permeability to Horseradish Peroxidase Across Cerebral Vessels in the Rat After Portocaval Anastomosis

Enhanced Permeability to Horseradish Peroxidase Across Cerebral Vessels in the Rat After Portocaval Anastomosis

Intracellular channels as a route for protein passage in the capillary endothelium of the shark brain

Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey

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