ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
A Biophysical Model for Cytotoxic Cell Swelling.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 78 citations in OpenAlex.
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Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in conditions of low energy supply, as observed in cerebral ischemia. Our model contains Hodgkin-Huxley-type ion currents, a recently discovered voltage-gated chloride flux through the ion exchanger SLC26A11, active KCC2-mediated chloride extrusion, and ATP-dependent pumps. The model predicts changes in ion gradients and cell swelling during ischemia of various severity or channel blockage with realistic timescales. We theoretically substantiate experimental observations of chloride influx generating cytotoxic edema, while sodium entry alone does not. We show a tipping point of Na SIGNIFICANCE STATEMENT: Cytotoxic edema most commonly results from energy shortage, such as in cerebral ischemia, and refers to the swelling of brain cells due to the entry of water from the extracellular space. We show that the principle of electroneutrality explains why chloride influx is essential for the development of cytotoxic edema. With the help of a biophysical model of a single neuron, we show that a tipping point of the energy supply exists, below which the cell volume rapidly increases. We simulate realistic time courses to and reveal critical components of neuronal swelling in conditions of low energy supply. Furthermore, we show that, after transient blockade of the energy supply, cytotoxic edema may be reversed by temporary blockade of Na
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