In rats experimental brain tumors were produced by intracerebral implantation of a glioma cell clone. Peritumorous edema was investigated by light and electron microscopy, using exogenous tracers [human serum albumin (HSA), horseradish peroxidase] and immuno-histochemical methods for localization of endogenous serum proteins. An infiltration by serum proteins was observed in peritumoral grey and white matter. Peroxidase was found in pinocytotic vesicles of vascular endothelial cells, in pericytes and diffusely in the extracellular space. High concentrations of endogenous rat serum proteins and exogenous human serum albumin were also found in neurons of the grey matter and in oligodendrocytes of the white matter. A cellular uptake of extravasated proteins, therefore, may contribute to edema resolution.

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PubMed1984

Experimental brain tumors and edema in rats. II. Tumor edema.

Experimentally induced brain tumors in rats with the morphological characteristics of low differentiated gliomas were investigated with special consideration of the distribution of extravasated serum proteins within the tumor itself. Protein extravasation across tumor vessels occurs by pinocytotic vesicles which enclose serum proteins at the luminal surface of the endothelial cells. These vesicles move to the abluminal cell surface where proteins are released after fusion between vesicles and the cell membrane. Serum proteins then spread through the extracellular space from where they are taken up in tumor cells by pinocytosis. They are then transmitted to and digested by lysosomes in which acid phosphatase activity could be demonstrated. Tracer studies (human serum albumin, horseradish peroxidase) revealed that proteins reach the lysosomes 15 min after systemic application. The cellular content of tracers is variable even when systemic circulation has lasted 120 min.

Animals↗

PubMed1983

The effect of dexamethasone on serum protein extravasation and edema development in experimental brain tumors of cat.

Experimental brain tumors were produced in 20 cats by stereotaxic xenotransplantation of a blastomatous glial cell clone into the internal capsule of the left hemisphere. Ten of these animals were treated after 2 weeks with a single injection of 10 mg dexamethasone in crystalline suspension. Three weeks after xenotransplantation vascular permeability was studied by electron microscopy with horseradish peroxidase as the barrier tracer (four animals), and extravasation of serum proteins was visualized by immunohistochemistry, using an image processing system (16 animals). In animals used for immunohistochemistry, the water content of peritumoral brain tissue was also determined. In both treated and untreated animals, spherical tumors with a diameter of about 10 mm were present at the implantation site. Extravasation of horseradish peroxidase was detected only in the tumor, but there was accumulation of serum proteins both in the tumor and the peritumoral white matter. Edema, in consequence, originated mainly in the tumor from where it spread into the surrounding brain tissue. Corticosteroid therapy reduced the water content of peritumoral brain tissue but did not affect increased barrier permeability of tumor vessels, and only slightly improved peritumoral accumulation of serum proteins. It is concluded that amelioration of tumor edema by corticosteroids cannot result solely from tightening of the blood-brain barrier to circulating macromolecules but must be due to an active restoration of cerebral water homeostasis despite persisting serum protein extravasation.

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PubMed1982

Immunochemical method for quantitative evaluation of vasogenic brain edema following cold injury of rat brain.

An immunochemical method is described for quantitative assessment of serum proteins and hemoglobin content in brain tissue homogenates. Using a combination of affinity chromatography and radioimmunoassay, the sensitivity of the method is 50 ng hemoglobin and 100 ng serum protein per assay, respectively. The method was used to measure cerebral hematocrit, blood volume and serum protein extravasation in rat brain at various times following cold injury. In control rats cerebral blood volume was 6.88 +/- 0.15 ml/100 g and cerebral hematocrit 26.4 +/- 0.86% (means +/- S.E.). Following cold injury blood volume did not significantly change, but there was a gradual increase of extravasated serum proteins, reaching a maximum of 21.54 +/- 2.76 mg/g d.w. after 8 hours. Thereafter protein content gradually declined, but even after 64 h it was distinctly increased. Protein extravasation was partly dissociated from the increase of brain water and sodium which reached a maximum already after 2 h and which normalized within 32 and 64 h, respectively. It is concluded that edema fluid associated with cold injury is not simply an ultrafiltrate of blood serum but consists of cytotoxic and vasogenic components which follow a different time course both during formation and resolution of edema.

Animals↗

PubMed1982

Investigations on vasogenic and cytotoxic brain edema, comparing results from X-ray microanalysis and flame photometry.

In these studies vasogenic brain edema has been induced by implantation of rat glioma cells RGI 2.2 into BD-IX rats while cytotoxic edema pas produced by permanent regional ischemia in the mongolian gerbil. In the gerbil sodium concentration was raised from 201 meq/kg d.w. (dry weight) [p/b (peak/background) = 0] to 269 meq/kg d.w. (p/b = 0.25; 2 hours) and 651 meq/kg d.w. [p/b = 0.71; 24 hours), whereas potassium concentration decreased from 373 meq/kg d.w. (p/b = 1.69) to 337 meq/kg d.w. (p/b = 1.65) and 152 meq/kg d.w. (p/b = 0.53). In the rat tumor sodium and potassium concentrations were 279 meq/kg d.w. (p/b = 0.44) and 510 meq/kg d.w. (p/b = 1.94). Non-tumorous tissue contained 237 meq/kg d.w. (p/b = 0) and 517 meq/kg d.w. (p/b = 1.98). In addition X-ray microanalysis could show that chlorine behaves like sodium, whereas the concentration of phosphorus and sulphur remains nearly constant. X-ray microanalysis in this case proved to be useful in the localization and quantification of different elements. The main disadvantage, however, is the reduced sensitivity for light elements, e.g. sodium, which cannot be determined in normal brain.

Animals↗

PubMed1981

Evaluation of vasogenic edema in experimental brain tumors by cathodoluminescence and fluorescence microscopy.

Cathodoluminescence and fluorescence microscopy have been used to study vasogenic edema in experimentally induced brain tumors in rats. Both methods are suited for the demonstration of FITC- or TRITC-coupled antiserum, and thus allow the evaluation of serum protein extravasation. Cathodoluminescence is more time consuming and laborious than fluorescence microscopy, but it has distinct advantages: Contrast enhancement improves the differentiation between certain cell types, and the higher resolution of the scanning electron microscope allows the identification of subcellular regions which cannot be recognized by conventional fluorescence microscopy.

Animals↗

PubMed1981

Experimental brain tumors and edema in rats. I. Histology and cytology of tumors.

In this study an experimental intracerebral tumor has been investigated with special consideration of structures, which may be involved in edema production and/or resolution. For this purpose a cloned tumor cell line (RG1 2.2) has been injected stereotactically into the brain of BD-IX rats. The tumor has some characteristics in common with low differentiated oligodendroglioma in men. A honeycomb architecture may be seen in the center of the tumor. It is built up by rounded or elongated cells, which can be impregnated in parts. In the central area, cells exhibit a voluminous digestive apparatus, composed of dictyosomes, vesicles, and some vacuoles with a membranaceous or homogeneous content. Tumor cells in the periphery show large processes and a small digestive apparatus. The sinusoidal tumor vessels are composed of an endothelium with many vesicles but no openings.

Animals↗

PubMed1980

[Freeze-etch studies of the chick embryonic skin with special consideration of cell junctions (author's transl)].

The skin of the quail embryo has been investigated microscopically with the help of freeze-etched preparations and the thin section method. On the 11th day of hatching the epidermis consists of the stratum basale and the periderm. They are not keratinized and do not differ concerning their cell junctions. Desmosomes have particles on both fracture faces with a diameter of 8 to 10 nm. Gap junctions consist of particles (5 to 8 nm) on P-face and depressions on E-face. Tight junctions are always small; they consist of spreaded ridges on the cytoplasmic face and grooves on the extracellular face. On the 14th day of hatching the stratum basale is keratinized in part in the outer layers and the periderm has been replaced by the fully keratinized stratum corneum. In the inner layers of the stratum basale cell junctions are identical with the epidermal cells on the 11th day of hatching. In the layers there are additional connexions of desmosomes and keratin fibrils. Tight junctions are absent in the stratum corneum. The size and frequency of gap junctions and desmosomes as well as the number of membrane-associated particles are reduced in comparison to the stratum basale.

Animals↗