title: Endothelial activation and chemoattractant expression are early processes in isolated blast brain injury.
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.
authors.affiliation: University Department of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Box 93, Cambridge, CB2 0QQ, UK, jer56@cam.ac.uk.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Risdall
authors.forename: Alun J
authors.initials: AJ
authors.lastname: Carter
authors.forename: Emrys
authors.initials: E
authors.lastname: Kirkman
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Watts
authors.forename: Christopher
authors.initials: C
authors.lastname: Taylor
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D004921:Erythropoietin / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006439:Hemodynamics; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: C491766:Ccl2 protein, rat; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016207:Cytokines; D016023:Integrins; D004921:Erythropoietin