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Glial swelling during extracellular acidosis in vitro
1Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University, München, Federal Republic of Germany.
Stroke
|March 1, 1988
Summary
Extracellular acidosis in the brain penumbra triggers cytotoxic cell swelling below pH 6.8. This swelling, mediated by ion exchange mechanisms, can be prevented by blocking sodium influx.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Acidosis, both intracellular and extracellular, impacts brain tissue outcomes in cerebral ischemia.
- Extracellular acidosis in the penumbra zone is a critical factor in cytotoxic cell swelling.
Purpose of the Study:
- To investigate the role of extracellular acidosis in the penumbra zone on the formation of cytotoxic cell swelling in vitro.
- To identify the mechanisms and thresholds involved in acidosis-induced cell swelling.
Main Methods:
- C6 glioma cells and primary cultured astrocytes were acidified to pH 6.2.
- Cell volume changes were measured using flow cytometry with hydrodynamic focusing.
- The effects of amiloride, acetazolamide, HEPES buffer, and choline chloride (replacing Na+) were assessed.
Main Results:
- A threshold pH of 6.8 was identified for inducing cell swelling.
- Cell swelling occurred as an all-or-nothing phenomenon below this threshold, reaching 115-118% of normal size.
- Swelling was attenuated by amiloride, acetazolamide, and HEPES buffer, and completely prevented by replacing extracellular Na+ with choline chloride.
Conclusions:
- Acidosis-induced glial swelling is significantly mediated by Na+/H+ and Cl-/HCO3- exchange mechanisms.
- Activation of the Na+/H+ antiporter attempts to maintain intracellular pH at the cost of cell volume.
- These findings highlight the critical role of ion transport in cerebral ischemia-related cell swelling.