(A) Pretrauma brain water content (naive) is approximately 77.5% and comparable in all genotypes; sham operation (striped bars) does not induce significant changes of brain water content. Twenty-four hours after CCI, brain water content in the traumatized (right) hemisphere is significantly increased compared to the respective controls; in homozygous S218L mutant mice (dark gray bars) brain edema formation is significantly more pronounced than in wild-type (WT; white bars) and S218L heterozygous mutant mice (light gray bars). Heterozygous animals, in contrast, showed no difference to WT mice. In the contralateral/nontraumatized hemisphere only homozygous S218L mutant mice had a significant increase in brain water content. As in the traumatized hemisphere, brain water content was significantly higher in homozygous S218L mutants than in WT and heterozygous S218L mutant mice (sham/naive: n = 5–8/group; S218L hom./het.: n = 15–18 each; WT: n = 16; median ± 95% confidence interval, *p < 0.05, **p < 0.005 vs. naive brain water content, analysis of variance [ANOVA] on ranks). (B) In the R192Q strain, brain water content was within normal limits in naive and sham-operated animals; 24 hr after CCI, however, it was significantly increased in homozygous mutant mice (dark gray bars) in both hemispheres compared to WT (white bars) (Sham/naive: n = 4–5/group; R192Q hom.: n = 6; WT: n = 9; median ± 95% confidence interval, *p < 0.05, rank sum test). (C) Intracranial pressure (ICP) 24 hr after trauma was significantly elevated in S218L homozygous mice (left panel, dark gray bar) compared to WT (white bar) and heterozygous mutant mice (light gray bar); in the R192Q strain, ICP tended to be higher in mutant animals (right panel, dark gray bar) than in their WT littermates (white bar; S218L het.: n = 15; S218L hom.: n = 7; S218L WT: n = 15; R192Q hom.: n = 7; R192Q WT: n = 7; median ± 95% confidence interval, *p < 0.005, ANOVA on ranks).