Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice
Open Access
- 23 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Neuroinflammation
- Vol. 9 (1), 17
- https://doi.org/10.1186/1742-2094-9-17
Abstract
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.Keywords
This publication has 48 references indexed in Scilit:
- Inflammatory mechanisms in ischemic stroke: role of inflammatory cellsJournal of Leukocyte Biology, 2010
- Administration of S-nitrosoglutathione after traumatic brain injury protects the neurovascular unit and reduces secondary injury in a rat model of controlled cortical impactJournal of Neuroinflammation, 2009
- Neutralization of interleukin‐1β modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in miceEuropean Journal of Neuroscience, 2009
- Neutrophil secretion products pave the way for inflammatory monocytesBlood, 2008
- Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injuryJournal of Neuroinflammation, 2008
- Neutrophil Infiltration Increases Matrix Metalloproteinase-9 in the Ischemic Brain after Occlusion/Reperfusion of the Middle Cerebral Artery in RatsJournal of Cerebral Blood Flow & Metabolism, 2003
- Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss, following traumatic brain injury in the ratJournal of Neuroscience Research, 1998
- Early White Blood Cell Dynamics after Traumatic Brain Injury: Effects on the Cerebral MicrocirculationJournal of Cerebral Blood Flow & Metabolism, 1997
- Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.Stroke, 1994
- THE ASSOCIATION OF LEUKOCYTES WITH SECONDARY BRAIN INJURYThe Journal of Trauma and Acute Care Surgery, 1993