Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 32, Issue 9, Pages 1810-1819Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2012.101
Keywords
cerebral ischemia; inflammation; interleukin-1 receptor antagonist; neutroprotection; risk factors; therapy
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Funding
- MRC
- European Union [201024, 202213]
- Biotechnology and Biological Sciences Research Council [BB/F011350/1, BBS/E/D/20251969] Funding Source: researchfish
- Medical Research Council [G0802001] Funding Source: researchfish
- BBSRC [BB/F011350/1, BBS/E/D/20251969] Funding Source: UKRI
- MRC [G0802001] Funding Source: UKRI
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Many neuroprotective agents have been effective in experimental stroke, yet few have translated into clinical application. One reason for this may be failure to consider clinical comorbidities/risk factors in experimental models. We have shown that a naturally occurring interleukin-1 receptor antagonist (IL-1Ra) is protective against ischemic brain damage in healthy animals. However, protective effects of IL-1Ra have not been determined in comorbid animals. Thus, we tested whether IL-1Ra protects against brain injury induced by experimental ischemia in aged JCR-LA (corpulent) rats, which have clinically relevant risk factors. Male, aged, lean, and corpulent rats exposed to transient (90 minutes) occlusion of the middle cerebral artery (tMCAO) were administered two doses of IL-1Ra (25 mg/kg, subcutaneously) during reperfusion. Brain injury and neuroinflammatory changes were assessed 24 hours after tMCAO. Our results show that IL-1Ra administered at reperfusion significantly reduced infarct volume measured by magnetic resonance imaging (50%, primary outcome) and blood-brain barrier disruption in these comorbid animals. Interleukin-1Ra also reduced microglial activation, neutrophil infiltration, and cytokines levels in the brain. These data are the first to indicate that IL-1Ra protects against ischemic brain injury when administered via a clinically relevant route and time window in animals with multiple risk factors for stroke. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1810-1819; doi:10.1038/jcbfm.2012.101; published online 11 July 2012
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