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Here, we have identified a potential driver of oedema: the negatively charged molecules fixed within cells. This fixed charge density (FCD), once exposed, could increase ICP through the Donnan effect. We have shown that metabolic processes and membrane integrity are required for concealing this FCD as slices of rat cortex swelled immediately (within 30\u2009min) following dissection if treated with 2 deoxyglucose + cyanide (2DG+CN) or Triton X-100. Slices given ample oxygen and glucose, however, did not swell significantly. We also found that dead brain tissue swells and shrinks in response to changes in ionic strength of the bathing medium, which suggests that the Donnan effect is capable of pressurizing and swelling brain tissue. As predicted, a non-ionic osmolyte, 1,2 propanediol, elicited no volume change at 2000\u00d710\n                    <jats:sup>\u22123<\/jats:sup>\n                    \u2009osmoles\u2009l\n                    <jats:sup>\u22121<\/jats:sup>\n                    (Osm). Swelling data were well described by triphasic mixture theory with the calculated reference state FCD similar to that measured with a 1,9 dimethylmethylene blue assay. Taken together, these data suggest that intracellular fixed charges may contribute to the driving forces responsible for brain\u00a0swelling.\n                  <\/jats:p>","DOI":"10.1098\/rsta.2009.0223","type":"journal-article","created":{"date-parts":[[2010,1,4]],"date-time":"2010-01-04T03:48:12Z","timestamp":1262576892000},"page":"585-603","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Fixed negative charge and the Donnan effect: a\u00a0description of the driving forces associated with brain tissue swelling and\u00a0oedema"],"prefix":"10.1098","volume":"368","author":[{"given":"Benjamin S.","family":"Elkin","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Columbia University, New\u00a0York,\u00a0NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Shaik","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Columbia University, New\u00a0York,\u00a0NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Barclay","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Columbia University, New\u00a0York,\u00a0NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2010,2,13]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.2746371"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490110103"},{"key":"e_1_3_2_4_1","first-page":"261","article-title":"Modulation of aquaporin-4 water transport in a model of TBI","volume":"86","author":"Amorini A. 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