Schwellung und Schädigung von Nerven- und Gliazellen durch Azidose
| Autor: | F. Staub, J. Peters, J. Haberstok, B.-M. Mackert, Alexander Baethmann, Oliver Kempski |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Programmed cell death
medicine.medical_specialty medicine.diagnostic_test business.industry General Medicine Pharmacology Critical Care and Intensive Care Medicine Surgery Flow cytometry Anesthesiology and Pain Medicine Cell culture Edema Emergency Medicine medicine Cytotoxic T cell Viability assay medicine.symptom business Homeostasis Acidosis |
| Zdroj: | AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie. 29:203-209 |
| ISSN: | 1439-1074 0939-2661 |
| Popis: | Objective Development of acidosis is a prominent pathophysiological factor in acute cerebral disorders, such as ischaemia or severe brain trauma. The impairment of the acid-base state in brain parenchyma among others is involved in the development of brain oedema, eventually leading to irreversible damage of neurons and glial cells. In the present study the pathophysiological role of acidosis for cytotoxic cell swelling and damage of glial and neuronal cells was investigated in vitro under conditions found in the ischaemic penumbra in vivo--the still viable perifocal border zone surrounding an infarct with elevated interstitial K(+)- and H(+)-concentrations. Assessment of cell swelling by acidosis was combined with experiments on underlying mechanisms as a basis for therapeutical interventions to inhibit cytotoxic brain oedema in vivo. Methods C6 glioma cells, astrocytes from primary culture, as well as Neuro-2A cells were cultivated, harvested and suspended as single cells under continuous control of pH, pO2, and temperature according to a standard procedure. Cell volume and cell viability were quantified by flow cytometry. Acidosis was induced by isotonic sulfuric- or lactic acid, respectively. Results Acidification of the medium led to cell swelling once pH fell below 7.0. Cell viability, however, was not affected by the increasing acidosis down to pH 6.2, while pH 5.6 or below was associated with cell death dependent on the duration of exposure. Acidosis-induced cell swelling was attenuated or completely inhibited by blocking of ion exchange mechanisms, such as the Na+/H(+)-antiporter, or elimination of Na+ ions from the medium. Conclusion The present results provide new information on the nature of cytotoxic cell swelling and damage in central nervous system by acidosis under consideration of underlying mechanisms. Accordingly, acidosis-induced cell swelling is attributable to activation of ion exchange mechanisms, such as the Na+/H(+)- and Cl-/HCO3(-)-antiporter, in order to maintain a normal cellular acid-base state. This compensation process, however, is associated with the loss of cell volume control by net uptake of osmotic active solutes. Consequently, cell swelling occurring under these conditions is a result of regulatory mechanisms to defend homoeostasis rather than a consequence of cytotoxic cell damage. If cell swelling is inhibited by appropriate treatment, care should be exercised not to enhance the vulnerability of the nerve and glial cells. |
| Databáze: | OpenAIRE |
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