title: Inflammation and brain injury: acute cerebral ischaemia, peripheral and central inflammation.
abstract: Inflammation is a classical host defence response to infection and injury that has many beneficial effects. However, inappropriate (in time, place and magnitude) inflammation is increasingly implicated in diverse disease states, now including cancer, diabetes, obesity, atherosclerosis, heart disease and, most relevant here, CNS disease. A growing literature shows strong correlations between inflammatory status and the risk of cerebral ischaemia (CI, most commonly stroke), as well as with outcome from an ischaemic event. Intervention studies to demonstrate a causal link between inflammation and CI (or its consequences) are limited but are beginning to emerge, while experimental studies of CI have provided direct evidence that key inflammatory mediators (cytokines, chemokines and inflammatory cells) contribute directly to ischaemic brain injury. However, it remains to be determined what the relative importance of systemic (largely peripheral) versus CNS inflammation is in CI. Animal models in which CI is driven by a CNS intervention may not accurately reflect the clinical condition; stroke being typically induced by atherosclerosis or cardiac dysfunction, and hence current experimental paradigms may underestimate the contribution of peripheral inflammation. Experimental studies have already identified a number of potential anti-inflammatory therapeutic interventions that may limit ischaemic brain damage, some of which have been tested in early clinical trials with potentially promising results. However, a greater understanding of the contribution of inflammation to CI is still required, and this review highlights some of the key mechanism that may offer future therapeutic targets.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Denes
authors.forename: P
authors.initials: P
authors.lastname: Thornton
authors.forename: N J
authors.initials: NJ
authors.lastname: Rothwell
authors.forename: S M
authors.initials: SM
authors.lastname: Allan
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D009457:Neuroglia / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines