Deficiency of CD18 gene reduces brain edema in experimental intracerebral hemorrhage in mice

Abstract

Experimental studies of intracerebral hemorrhage (ICH) point toward leukocytes as a major contributor to ICH-induced brain injury. Leukocyte and endothelial cell adhesion molecules are responsible for injurious neutrophil-endothelial cell interactions in vasculature. Since deficiency of leukocyte-expressed CD18 protects against ischemia-re-perfusion injury, we hypothesized that such deficiency may have similar effect in ICH-induced injury. Our aim was to investigate whether CD18 deficiency affords neuroprotection by decreasing ICH-induced brain injury, thereby improving neurological function and reducing mortality. A total of 20 males wild-type CD18+/+ mice and 12 CD18-/- knockout mice were used in our study. ICH was induced by collagenase injection. Mortality, neurological function, and brain edema were measured at 24 h after ICH. Data were analyzed by ANOVA, Chi-square, and Student t-test. Differences ofp<0.05 were considered statistically significant. Our study showed that the increase in brain water content caused by ICH was significantly smaller in CD18 knockout mice compared with wild-type mice (p<0.05, Student t-test). This result correlated with a tendency toward improvement of neurological function and a decrease in mortality. We conclude that CD18 deficiency significantly reduces brain edema after ICH, which corresponds with a trend toward reduction in neurological deficit and mortality. © 2008 Springer-Verlag.