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Endothelial Activation and Chemoattractant Expression are Early Processes in Isolated Blast Brain Injury

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Abstract

Blast injuries are an increasing problem in military conflicts and terrorist incidents. Blast-induced traumatic brain injury has risen to prominence and represents a specific form of primary brain injury, with sufficiently different physical attributes (and possibly biological consequences) to be classified separately. There is increasing interest in the role of blast in initiating inflammatory responses, which may be linked to the pathological processes seen clinically. Terminally anaesthetised rats were exposed to a blast wave directed at the cranium, using a bench-top blast wave generator. Control animals were not exposed to blast. Animals were killed after 8 h, and the brains examined for evidence of an inflammatory response. Compared to controls, erythropoietin, endothelial integrins, ICAM and sVCAM, and the pro-inflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1) were significantly elevated. Other pro-inflammatory cytokines, including MIP-1α, were also detectable, but levels did not permit accurate quantification. Six inflammatory genes examined by qRT-PCR exhibited a biologically significant increase in activity in the blast-exposed animals. These included genes supporting chemokines responsible for monocyte recruitment, including MCP-1, and chemokines influencing T cell movement. Brain injury is usually accompanied by pathological neuro-inflammation. This study shows that blast brain injury is no exception, and the data provide important mechanistic clues regarding the drivers of such inflammation. Whilst this effect alone is unlikely to be responsible for the totality of consequences of blast brain injury, it suggests a mechanism that may be priming the cerebral inflammatory response and rendering cerebral tissue more susceptible to the deleterious effects of systemic inflammatory reactions.

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Acknowledgments

The majority of this work was funded by the Human Dimension and Medical Sciences Domain of the UK Ministry of Defence Science and Technology Research Programme. The cytokine analysis was funded by the Royal Centre for Defence Medicine Research Fund. DKM is supported by a Senior Investigator award from the National Institute for Health Research UK.

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Authors and Affiliations

  1. University Department of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Box 93, Cambridge, CB2 0QQ, UK

    Jane E. Risdall & David K. Menon

  2. Biomedical Sciences, Bldg 4, Dstl Porton Down, Salisbury, SP4 0JQ, UK

    Alun J. Carter & Christopher Taylor

  3. Biomedical Sciences, Bldg 245, Dstl Porton Down, Salisbury, SP4 0JQ, UK

    Emrys Kirkman & Sarah A. Watts

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  1. Jane E. Risdall
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Correspondence to Jane E. Risdall.

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Risdall, J.E., Carter, A.J., Kirkman, E. et al. Endothelial Activation and Chemoattractant Expression are Early Processes in Isolated Blast Brain Injury. Neuromol Med 16, 606–619 (2014). https://doi.org/10.1007/s12017-014-8313-y

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