Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice

Background: brain edema as a result of secondary injury following traumatic brain injury (tbi) is a major clinical concern. neutrophils are known to cause increased vascular permeability leading to edema formation in peripheral tissue,but their role in the pathology following tbi remains unclear.methods: in this study we used controlled cortical impact (cci) as a model for tbi and investigated the role of neutrophils in the response to injury. the outcome of mice that were depleted of neutrophils using an anti-gr-1 antibody was compared to that in mice with intact neutrophil count. the effect of neutrophil depletion on blood-brain barrier function was assessed by evan's blue dye extravasation,and analysis of brain water content was used as a measurement of brain edema formation (24 and 48 hours after cci). lesion volume was measured 7 and 14 days after cci. immunohistochemistry was used to assess cell death,using a marker for cleaved caspase-3 at 24 hours after injury,and microglial/macrophage activation 7 days after cci. data were analyzed using mann-whitney test for non-parametric data.results: neutrophil depletion did not significantly affect evan's blue extravasation at any time-point after cci. however,neutrophil-depleted mice exhibited a decreased water content both at 24 and 48 hours after cci indicating reduced edema formation. furthermore,brain tissue loss was attenuated in neutropenic mice at 7 and 14 days after injury. additionally,these mice had a significantly reduced number of activated microglia/macrophages 7 days after cci,and of cleaved caspase-3 positive cells 24 h after injury.conclusion: our results suggest that neutrophils are involved in the edema formation,but not the extravasation of large proteins,as well as contributing to cell death and tissue loss following tbi in mice. © 2012 kenne et al; licensee biomed central ltd.