Volume and Metabolism of C-6 Glioma Cells Suspended in Hypotonic Medium: An In-Vitro Model to Study Cytotoxic Brain Edema
The mechanisms effective in the development of cytotoxic edema are far from being understood as opposed to the pathogenesis of vasogenic edema. The multitude of simultaneous changes occurring in brain in-vivo after a cytotoxic insult (i.e. breakdown of intra-extracellular ion-gradients, release of metabolites, and eventually of toxic substances into the extracellular space, acidosis, anoxia, and dysregulation of neurotransmitter homeostasis, etc.) obscures the analysis of this type of edema. It is impossible to control, or monitor in-vivo these factors simultaneously. Therefore, an in-vitro model has been developed in order to investigate cell volume control under pathophysiological conditions and to study the role of suspected brain edema mediators3,8. For that purpose, cell volume changes of suspended glial cells were measured under strictly controlled extracellular conditions. In additional experiments environmental parameters, as e.g. PO2, pH, osmolarity and ionic composition were varied systematically. Oxygen consumption was studied as a measure of cellular energy metabolism. Intracellular electrolyte concentrations were determined to analyze potential mechanisms for the observed changes of cell volume. This is a report on the swelling behavior of C-6 glioma cells serving as a model for cells with glial characteristics under hypoosmotic stress. Osmotic edema is not only of clinical significance (e.g. in water intoxication or iatrogenic overhydration in hyperosmolar coma) but it also proved to be an appropriate model to test the regulatory mechanisms maintaining a constant cell volume.
KeywordsCell Volume Glioma Cell Regulatory Volume Decrease Ehrlich Ascites Tumor Cells6 Cell Volume Regulation
Unable to display preview. Download preview PDF.
- 3.Chaussy L, Baethmann A, Lubitz W: Electrical sizing of nerve and glial cells in the study of cell volume regulation. In: Cervos-Navarro J, Fritschka (Eds): Cerebral Microcirculation and Metabolism pp 29–40, Raven Press New York 29-40 (1981).Google Scholar
- 5.Gilles R: Intracellular free amino acids and cell volume regulation during osmotic stresses. In: Osmotic and Volume Regulation, Alfred Benzon Symposium XI, Jorgensen CB, Skadhauge E (Eds): Munksgaard (1978).Google Scholar
- 6.Hendil KB, Hoffmann EK: Cell volume regulation of Ehrlich asci-tes tumor cells. J Gen Physiol 84: 115–126 (1974).Google Scholar
- 8.Kempski O, Gross U, Baethmann A: An vitro model of cytotoxic brain edema: Cell volume and metabolism of cultivated glial-and nerve cells. Advanc Neurosurg 10: Springer Berlin (in press).Google Scholar
- 10.Meynaud A, Grand M, Fontaine L: Effect of naftidrofuryl upon energy metabolism of the brain. Arzneimittelforsch 23: 1431–1436 (1973).Google Scholar
- 11.Poggioli J, Mazet JL, Claret M: Régulation du volume des hépato-cytes isolés du Rat en milieu hypoosmotique. C.R. Acad Sc Paris 285: 1467–1470, Série D (1977).Google Scholar
- 12.Rosenberg HM, Shank BB, Gregg EC: Volume changes of mammalian cells subjected to hypotonic solutions in vitro: evidence for the requirement of a sodium pump for the shrinking phase. J Gen Physiol 80: 23–32 (1972).Google Scholar