Cerebral contusion and endothelial damages following neutrophil adhesion

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Cerebral contusion induces a tissue inflammatory response following neutrophil adhesion and migration into brain tissue, which may contribute to secondary cell injury processes in contusion and surrounding brain. In the present study, we investigated effects of immunosuppressants (Cyclosporin A, FK506) and anti-P-selectin antibody on contusion-induced edema formation and tissue damages, using a controlled cortical impact model of rat. The doze of 1 mg/kg FK506 significantly attenuated the contusion edema and subsequent brain damages (p<0.01). The dose of 10 mg/kg FK506, however, did not show such therapeutic effects. The cyclosporin A administration showed the tendency to reduce the brain damage, but the changes were not statistically significant. The administration of anti-P-selectin antibody immediately after the injury induction markedly attenuated the neutrophil accumulation, which was evaluated by histological studies and tissue myeloperoxidase activities, and the subsequent edema formation as well as necrosis formation (p<0.01). These findings suggest that activation of neutrophils contributes to contusion-induced secondary cell damages, and inhibition of such processes provides therapeutic effects for the treatments of cerebral contusion.