Effect of dexamethasone on glial fibrillary acidic protein in peritumorous edema of cats: A morphometric study

Abstract

In 54 cats experimental brain tumors were produced by xenotransplantation of the blastomatous glial cell clone RG2 into the internal capsule of the left hemisphere. Fifteen of these animals were treated with dexamethasone for 1 week and four animals for 2 h. The occurrence of glial fibrillary acidic (GFA) protein in tumor and peritumoral edema was studied by immunocytochemistry at intervals ranging between 3 and 35 days after implantation. High concentrations of GFA protein were present in giant and many of the larger tumor cells but not in small tumor cells. In peritumorous white matter it appeared in reactive astrocytes, where it reached its maximum 2 weeks after implantation. At this time, morphometric evaluation of GFA protein-positive areas revealed an increase from 0.095 +/- 0.035% to 5.17 +/- 1.42%. Application of dexamethasone for 1 week reduced this area to 1.67 +/- 0.57% (P less than 0.001). The results obtained demonstrate that the development of peritumorous edema is associated with considerable stimulation of GFA protein production which is inhibited by dexamethasone. Production of GFA protein by reactive astrocytes, in consequence, does not seem to be involved in the resolution process of peritumoral edema under dexamethasone therapy.

Effects of glucocorticoid and chemotherapy on the peritumoral edema and astrocytic reaction in experimental brain tumor

“…The histologic effects of tumor on the surrounding brain tissue were evaluated by the quantitative analysis of the local astrocytic reaction. Astrocytes respond to various kinds of brain lesion by hypertrophy and proliferation as well as an increase in GFAP content [4,16,17]. This reaction is supposedly induced by the extravasated serum components [16,18,19] or other materials in the edema fluid released from the damaged tissue [20,21].…”

Effect of dexamethasone on blood‐brain barrier in the normal mouse

“…This decrease was accompanied by a decrease in the number of HRP-containing small endothelial vesicles. These data suggest that dexamethasone influences cerebral edema by decreasing the permeability of the cerebral vasculature for macromolecules.Hedley-Whyte ET, Hsu DW: Effect of dexamethasone on blood-brain barrier in the normal mouse.Ann Neurol 19373-377, 1986 Dexamethasone reduces increased intracranial pressure resulting from cerebral edema associated with brain tumors and pseudotumor [7, 12, 16,23,26,29,34,39, 451 [24] are each associated with a decrease in the permeability of the blood-brain barrier for macromolecules suggests that dexamethasone might also affect the normal blood-brain barrier. Since the mouse brain normally has a number of horseradish peroxidase-permeable arteries (or arterioles) [ l 5 , 17, 46, 471, and its normal brain water content is decreased by hydrocortisone treatment 14 11, the normal mouse seemed to be a suitable model to study the effect of dexamethasone on the normal blood-brain barrier.…”

Tumour necrosis factor receptor superfamily member 9 (TNFRSF9) is up‐regulated in reactive astrocytes in human gliomas

“…Considering that the CNS is an immunoprivileged organ due to the blood‐brain barrier and that only a few infiltrating lymphocytes were detected in our specimens, the finding that intracranial tumours were sensitive to systemic mAb treatment raises the question of whether or not other specialized resident immune cells, such as microglia, or alternative members of the brain microenvironment increase distinct anti‐tumoural immune response. In addition, it has to be considered that a preoperative steroid treatment that avoids peritumoural oedema and is often applied in glioblastoma patients, might lead to a decreased glial reactivity and a diminished lymphocytic invasion [24–27]. In vitro studies revealed that TNFRSF9 is up‐regulated by astrocytes upon stimulation with the Ca(2+)‐binding protein S100B that is frequently increased during CNS pathologies [28].…”