Cold injury-induced swelling of brain and other tissues: its molecular mechanism

Isolated mouse brain, kidney, and other tissues were incubated for from one to several days at 4 degrees C in isotonic solutions containing varying mixtures of sucrose and NaCl (or Na2SO4, LiCl, Li2SO4, MgSO4). The ischemic, cold-injured tissues swelled in proportion to the concentration of NaCl or LiCl. They swelled less in Na2SO4 and Li2SO4 and they swelled even less and/or shrank in MgSO4 or sucrose. It was shown that in the presence of about 100 mM NaCl, the degree of swelling follows inversely the level of ATP present in the cells. The data were interpreted using the theory of cell swelling based on the association-induction hypothesis: NaCl- and LiCl-induced swelling in injured tissues and KCl-induced swelling in normal tissues, were both explained as the consequence of the dissociation of the volume-restraining effects of salt linkages among cell proteins. The depletion of ATP and the consequent increase of electron density or c-value of the fixed anionic groups turns NaCl (ineffective in causing swelling of normal tissues) into a fully effective agent for causing swelling of the injured tissues.