Dynamics and pattern of ultrastructural alterations induced by quinolinic acid in organotypic culture of rat hippocampus.
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Biomedical subjects
Publications and source records attributed to E Matyja.
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The purpose of this study was to develop a mathematical model which would be easy to use and which could provide an objective classification of experimental brain tumors. 250 brain tumors (glioblastomas, astrocytomas, astroblastomas, oligodendrogliomas, ependymomas, fibrosarcomas and giant cell sarcomas), induced in mice, were studied. In every case the same 50 histological characteristics were analyzed. For astroblastomas, oligodendrogliomas and ependymomas the diagnosis given by the neuropathologist and that given by the computer corresponded in 100% of the cases. However, some fibrosarcomas and giant cell sarcomas were not grouped in the same diagnostic category by the computer as that assigned by the neuropathologist. Thus an overall efficiency of 94.35% was obtained. This simple and efficient system of classification allows for further statistical analyses and makes it possible to correlate the results presented by different authors, thus providing for unity in all those works concerned with experimental neurooncology.
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Injury to the nervous tissue was studied in the electron microscope after unilateral stereotaxic injection of kainic acid into the rat striatum. Progressive degeneration of neurons and selective injury of dendritic processes was noted. On the third day of the experiment three types of degeneration of the postsynaptic elements could be distinguished: shrinkage of the dendritic spines and swelling or increase of electron density of the postsynaptic dendrites. Most axonal boutons did not show morphological changes.
Glial changes that follow kainic acid administration were studied in the rat neostriatum at many different time intervals after the lesion, both in the animal model of Huntington's chorea and in an organotypic culture of striatum. The glial reaction showed striking similarities between in vivo and in vitro conditions and resulted in extensive production and accumulation of gliofilaments leading to transformation of the protoplasmic type of astroglia into the fibrous type. The earliest ultrastructural study in vivo revealed severe swelling of the astrocytic cytoplasm and additional morphologic changes of cytoplasmic organelles, i.e., enlargement of mitochondria, dilation of rough endoplasmic reticulum, and presence of numerous vacuoles. The glial pathology progressed parallel to neuronal degeneration. The same reaction was observed in culture both in the explanted tissue in which neurons remained intact and in the distant outgrowth zone containing a pure population of glial cells. This study proved that kainic acid might act directly on astroglia cells and that glial changes were independent of neuronal damage. Because kainic acid is a structural analog of glutamate, the presented results may be interpreted to reflect changes in the metabolism of this amino acid occurring in astroglia independently of neuronal changes. This interpretation is consistent with the existence of two independent metabolic compartments of glutamate.
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Microdialysis was used to apply 1 mM N-methyl-D-aspartate (NMDA) for 20 min to the hippocampus of rabbits, control and pre-treated with GM1 ganglioside (im injections of 30 mg/kg for 3 d, twice a day). Concentrations of ionized Ca2+ and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha)-immunoreactive material in the dialyzates and 45Ca and [14C]sucrose efflux from the prelabeled hippocampus were determined. After 24 h, the morphology of the hippocampal neurons was examined. In control animals, the application of NMDA resulted in 25% decrease in Ca2+ concentration and in 1000% increase in 6-keto PGF 1 alpha concentration in the dialyzates. A 30% decrease in 45Ca efflux was accompanied by 20% increase in [14C]sucrose efflux, reflecting a corresponding reduction of the extracellular space volume. A degeneration of CA1 pyramidal neurons in the vicinity of a microdialysis probe was observed. In GM1-treated rabbits the NMDA-induced decrease in Ca2+ concentrations in the dialyzates was not reduced significantly, whereas a 70% stimulation of 45Ca efflux was noted, with a concomitant 40% reduction of 6-keto-PG F1 alpha release. NMDA-evoked increase in [14C]sucrose efflux did not differ from the control. In these animals CA1 neurons were well preserved. These results indicate that the pretreatment with GM1 results in activation of calcium extrusion from the NMDA-stimulated rabbit hippocampal neurons that alleviates destabilization of calcium homeostasis and reduces NMDA-evoked neuronal injury.
Giant cell glioblastoma (GCG-BM) with predominance of bizarre, multinucleated giant cells is a rare subtype of glioblastoma, however, its clinical behavior and histological features are still not fully understood. We report an unusual case of a heavily lipidized form of giant cell glioma corresponding mostly to GCGBM in a young patient with neurofibromatosis 1 (NF1). Histologically, the tumor revealed numerous characteristic histopathological features of giant cell glioblastoma including cellular pleomorphism with numerous giant tumor cells, pseudopalisades around necrotic foci and mitotic activity, accompanied by additional unique morphological elements such as massive lipidization of the neoplastic cells, abundant microcalcifications and angiomatous pattern of vascularization. Such aberrant morphology might be associated with the unusually long survival period of 12 years without clinical evidence of tumor recurrence. The coexistence of intracerebral heavily lipidized, calcified giant cell glioblastoma with NF1 has not been previously reported in literature.
Meningiomas exhibit a broad spectrum of differentiation potency corresponding to different histological subtypes. The separate secretory or lipomatous transformation of meningothelial cells is uncommonly encountered in meningiomas classified into distinct secretory or lipomatous variants. The coexistence of these two different histological subtypes is extremely rare. We report an exceptional case of secretory meningioma associated with extensive lipomatous component in a 58-year-old woman. CT scan and MRI of the brain showed a well-defined tumor mass in the right temporal lobe with areas of adipose tissue and extensive surrounding brain edema. Microscopically, the tumor was composed of two components: whorls of meningothelial cells with numerous PAS-positive hyaline inclusions (pseudopsammoma bodies) and numerous mature adipocyte-like cells. The presence of neutral fat was confirmed by oil-red-O staining. The hyaline inclusions and tumor cells surrounding them showed strong immunoreactivity for EMA and CEA. Ultrastructural findings confirmed both secretory and lipomatous differentiation of tumor cells. The majority of lipidized neoplastic cells shared the features of meningothelial cells and adipocytes. Our result supports the opinion that lipomatous component ought to be considered as an advanced lipidization of neoplastic meningothelial cells rather than true metaplastic transformation of meningothelial cells into mature fat tissue. The present case of meningioma demonstrates a unique coexistence of secretory and lipomatous meningothelial components, reflecting the multipotency of phenotypic transformation of primary meningothelial cells.
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