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  • 1
    ISSN: 1432-0533
    Keywords: Blood-brain barrier ; Hyperosmolar solutions ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Infusion of hypertonic solutions into the carotid artery is one method by which the blood-brain barrier (BBB) can be opened transiently in experimental animals. This technique has also been tried in clinical situations in which an enhanced uptake of intravenously injected chemotherapeutic drugs into the brain is desired. We have previously found that infusion of hypertonic mannitol or urea into the carotid artery of the rat, leading to a BBB opening, is associated with light microscopic signs of cellular damage in the brain parenchyma. An electron microscopic study has now been made to obtain more detailed information about the events taking place in the rat brain 1 to 72 h after an intracarotid infusion of hyperosmolar solution of mannitol. Toluidine blue-stained semithin epon sections were also available for high-resolution light microscopy of brain samples from urea-infused animals. Intravenously injected Evan's blue dye was used to confirm that BBB opening had occurred as a consequence of the carotid infusions. The infused hemispheres had numerous structural changes. The dominating light microscopic alteration was the presence of multifocal lesions in the gray or the white matter with closely packed microvacuoles causing status spongiosus. Ultrastructurally the microvacuoles corresponded to very pronounced watery swelling of astrocytic processes and to a minor degree to expansion of dendrites and axons. There was also a light or moderate perivascular astrocytic swelling. In the “spongy” lesions as well as occasionally in non-vacuolated parts of the cerebral cortex, there were collapsed electron-dense neurons with pronounced mitochondrial alterations such as severe swelling associated with rupture of christae. Rats with a survival period of 24 h or 72 h showed several disintegrating neurons and accumulation of macrophages. This study shows that carotid infusion of hypertonic mannitol in the rat may cause pronounced neuronal changes as well as multifocal astrocytic swelling. The severity of the nerve cell changes and the presence of macrophages indicate that some of the alterations are irreversible and thus, such a procedure may not be as safe as previously suggested.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Blood-brain barrier ; Vasogenic brain edema ; Plasma proteins ; Immunohistochemistry ; Hyperosmolar solutions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An immunohistochemical study was carried out on rat brain to determine if a transient opening of the blood-brain barrier (BBB), leading to extravasation of serum albumin, is also associated with exsudation and cellular uptake of fibronectin and fibrinogen. Both of them might exert important biological effects provided that they pass the BBB and come into contact with cells of the brain parenchyma. Hyperosmolar solutions of urea or mannitol were infused in the carotid artery for 30 s to open the BBB and the animals were killed at various time intervals thereafter. Formaldehyde-fixed, paraffin-embedded material was used for immunohistochemical demonstration of extravasated proteins by an avidin-biotin peroxidase technique. Multifocal, often confluent areas of widely different sizes with signs of albumin extravasation were observed both in the grey and the white matter of the cerebral hemispheres exposed to the hyperosmolar solutions. Much less pronounced changes were observed in rats given an intracarotid saline infusion alone. Immunoreactive material indicating extravasation of fibronectin and fibrinogen was present in the infused cerebral hemispheres but albumin immunoreactivity was much more widespread. Reaction product was observed in vascular walls, presumably in extracellular spaces and in nerve cells. Immunoreactivity in the perikaryon of neurons formed different patterns in various cells. Agranular type most probably represents accumulation of the proteins in lysosomal organelles after pinocytotic uptake into the neuron. The second so-calleddiffuse variety is presumably the result of a severe nerve cell injury with an uncontrolled leakage of proteins into the cytoplasm. Our results indicate that vascular walls, extracellular spaces, glial cells and neurons will be exposed to extravasated fibronectin and fibrinogen as well as to albumin and that antigenic sites in such compounds remain for a long period after the BBB opening. In addition, there are indications that carotid infusions of hyperosmolar solutions may cause nerve cell injuries in regions with BBB opening. These findings have obvious clinical and experimental significance.
    Type of Medium: Electronic Resource
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