The immune system in stroke: clinical challenges and their translation to experimental research.
J Neuroimmune Pharmacol. 2013-05-15; 8(4): 867-887
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1. J Neuroimmune Pharmacol. 2013 Sep;8(4):867-87. doi: 10.1007/s11481-013-9469-1.
Epub 2013 May 15.
The immune system in stroke: clinical challenges and their translation to
Smith CJ(1), Lawrence CB, Rodriguez-Grande B, Kovacs KJ, Pradillo JM, Denes A.
(1)Stroke and Vascular Research Centre, Institute of Cardiovascular Sciences,
University of Manchester, Manchester Academic Health Science Centre, Salford
Royal Foundation Trust, Salford M6 8HD, UK.
Stroke represents an unresolved challenge for both developed and developing
countries and has a huge socio-economic impact. Although considerable effort has
been made to limit stroke incidence and improve outcome, strategies aimed at
protecting injured neurons in the brain have all failed. This failure is likely
to be due to both the incompleteness of modelling the disease and its causes in
experimental research, and also the lack of understanding of how systemic
mechanisms lead to an acute cerebrovascular event or contribute to outcome.
Inflammation has been implicated in all forms of brain injury and it is now clear
that immune mechanisms profoundly influence (and are responsible for the
development of) risk and causation of stroke, and the outcome following the onset
of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with
respect to common comorbidities in stroke, have largely been ignored in
experimental studies. The main aim is therefore to understand interactions
between the immune system and brain injury in order to develop novel therapeutic
approaches. Recent data from clinical and experimental research clearly show that
systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or
infection – similar to stress and advanced age, are associated with dysregulated
immune responses which can profoundly contribute to cerebrovascular inflammation
and injury in the central nervous system. In this review, we summarize recent
advances in the field of inflammation and stroke, focusing on the challenges of
translation between pre-clinical and clinical studies, and potential
anti-inflammatory/immunomodulatory therapeutic approaches.
PMID: 23673977 [Indexed for MEDLINE]