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  • 1
    Digitale Medien
    Digitale Medien
    Cytofluorescence localization of adriamycin in the nervous system (1982)
    Springer
    Acta neuropathologica 58 (1982), S. 193-202 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Adriamycin ; Doxorubicin ; Blood-brain barrier ; Circumventricular organs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary By a fluorescence-microscopic technique the distribution of the antineoplastic anthracyclic compound adriamycin (doxorubicin) was determined in the brain of normal adult mice after intraventricular and arachnoidal injections. These experiments were carried out to circumvent the blood-brain barrier since there are indications that vascular permeability properties determine the extent to which the drug will spread into the brain after systemic administration. In line with this concept we found previously that after i.v. injection the drug leaks into circumventricular organs of the brain. These are special areas which have permeable vessels to a number of substances including adriamycin (Bigotte et al. 1982a). After intraventricular injection the nuclei of ependymal cells throughout the ventricular system contained intensely fluorescent orange-red material characteristic of adriamycin. A thin layer of the brain parenchyma adjacent to the ventricular walls showed fluorescent nuclei. In the corpus callosum, fascia dentata of the hippocampus, and the hypothalamic preoptic nuclei the drug penetrated deeper into the tissue, and the intensity of the drug-induced fluorescence was very high there. In the circumventricular organs two different patterns of intraventricularly injected adriamycin movement were revealed. The organum vasculosum of the lamina terminalis, the subcommissural organ, and the choroid plexus showed a very strong drug-induced nuclear fluorescence both within the parenchyma and in the covering ependyma. The median eminence, the subfornical organ, the postremal area, the neurohypophysis, and the pineal gland did not show any labeling of their parenchyma. The tanycyte ependyma lining the median eminence did not take up any tracer from the ventricular fluid. Adriamycin which passed into the leptomeninges labeled a few cells in the arachnoid as well as neurons and glial cells in the adjacent first and second cortical layers. The drug also penetrated into the optic tracts and nerves. In these areas a marked adriamycin-induced fluorescence was present in the nuclei of oligodendrocytes. Our study thus shows that when the blood-brain barrier is by-passed different types of neurons and glial cells have the capacity to take up and accumulate the drug in their nuclei. Adriamycin can spread into the periventricular parenchyma after intraventricular administration but its movement into the circumventricular organs differs considerably from one area to another. Knowledge about these phenomena is essential for future studies on the neurotoxic action of adriamycin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00690801
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  • 2
    Digitale Medien
    Digitale Medien
    Toxic effects of adriamycin on the central nervous system (1983)
    Springer
    Acta neuropathologica 61 (1983), S. 291-299 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Adriamycin ; Doxorubicin ; Neurotoxicity ; Blood-brain barrier ; Circumventricular organs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Recent experimental studies have shown that the cytotoxic antibiotic adriamycin (doxorubicin) after systemic administration can enter the so-called circumventricular organs (CVO) of the brain of the mouse. The present experiments were performed to find out whether such penetration of the brain is associated with signs of neurotoxic injury. For this purpose, light-and electron-microscopic observations were carried out on three of these organs: the neurohypophysis (NH), median eminence (ME), and postremal area (PA). Pronounced widening of the extracellular space indicating the presence of edema was present in all the regions, particulary in animals examined within 3 days of injection of the drug. Many degenerated axon terminals were observed in the NH and ME. The glial cells within these regions showed rarefaction of the nuclear chromatin, nucleolar segregation, and also cytoplasmic changes. The PA presented marked cellular changes resulting in degeneration of neurons, which was most evident 30 days after the injection. Hence, regions of the CNS outside the blood-brain barrier can be reached by adriamycin after systemic administration, and the drug can induce morphological changes there. The doses of the drug used in the present experiments were comparable to those given to patients for the treatment of malignant tumors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00692000
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  • 3
    Digitale Medien
    Digitale Medien
    Cytofluorescence localization of adriamycin in the nervous system (1982)
    Springer
    Acta neuropathologica 57 (1982), S. 121-129 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Adriamycin ; Doxorubicin ; Circumventricular organs ; Blood-brain barrier
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary By a fluorescence-microscopic technique the distribution of the antineoplastic glycoside, adriamycin (doxorubicin), was studied in the CNS of normal adult mice after i.v. injection. Doses comparable to those used in patients for the treatment of malignant diseases were used. The drug did not have access to areas of the brain within the blood-brain barrier but, except for the subcommissural organ, it was consistently localized in the nuclei of neurons and/or glial cells of the circumventricular organs (postremal area, subfornical organ, median eminence, neurohypophysis) as well as in cells of the choroid plexus and lamina cribrosa of the optic nerve. The nuclear fluorescence was accompanied by a less intense extracellular fluorescence when the survival time was shorter than 1 min after the injection. The fluorescence emitted by adriamycin was seen as early as 15 s after injection and showed its highest intensity at 1 and 15 min later. After 24 h fluorescence was no longer observed except for the ependymal zone of the median eminence. Our study thus shows that adriamycin passes from the blood into the nervous parenchyma in those areas of the brain located outside the blood-brain barrier. This finding raises the question whether in such regions there are any neurotoxicologic effects produced by the drug which have not yet been detected.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685379
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  • 4
    Digitale Medien
    Digitale Medien
    Cytofluorescence localization of adriamycin in the nervous system (1982)
    Springer
    Acta neuropathologica 57 (1982), S. 130-136 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Adriamycin ; Doxorubicin ; Bloodnerve barrier ; Peripheral nervous system (PNS)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary By a fluorescence-microscopic technique, the distribution of the antineoplastic glycoside adriamycin (doxorubicin) was studied in the peripheral nervous system (PNS) of normal adult mice after i.v. injection. Doses comparable to those used in patients for treatment of malignant diseases were used. The orange-red fluorescence of the drug was observed in dorsal root ganglia, in the trigeminal ganglia, and in the superior cervical sympathetic ganglia where it was preferentially accumulated in the nuclei of satellite cells. This nuclear labeling was a very quick process which occurred in the superior cervical ganglion within 15 s after the injection. Adriamycin-fluorescent nuclei were also observed in the suprarenal medulla. Fluorescent nuclei were present within the pre- and postganglionic sympathetic nerve trunks close to the superior cervical ganglion but not in the endoneurium of the trigeminal and the sciatic nerves or in the spinal nerve roots. In such structures labeled cells appeared in the connective tissue sheaths covering the nerves and the roots. No adriamycin-induced fluorescence was detected in the myenteric plexus of the intestine. Our study thus shows that i. v. injected adriamycin is distributed preferentially within areas of the PNS where the blood vessels are known to be highly permeable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685380
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