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Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats.

Pradillo, Jesus M; Denes, Adam; Greenhalgh, Andrew D; Boutin, Herve; Drake, Caroline; McColl, Barry W; Barton, Eleanor; Proctor, Spencer D; Russell, James C; Rothwell, Nancy J; Allan, Stuart M

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2012;.

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Abstract

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 advance online publication, 11 July 2012; doi:10.1038/jcbfm.2012.101.

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Manchester eScholar ID:
uk-ac-man-scw:165344
Created by:
Bentley, Deborah
Created:
24th July, 2012, 12:35:29
Last modified by:
Bentley, Deborah
Last modified:
24th July, 2012, 12:35:29

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