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• W2132453743 abstract "Background and purpose: Limited data on the brain penetration of potential stroke treatments have been cited as a major weakness contributing to numerous failed clinical trials. Thus, we tested whether interleukin‐1 receptor antagonist (IL‐1RA), established as a potent inhibitor of brain injury in animals and currently in clinical development, reaches the brain via a clinically relevant administration route, in experimental stroke. Experimental approach: Male, Sprague‐Dawley rats [either naïve or exposed to middle cerebral artery occlusion (MCAo)] were given a single s.c. dose of IL‐1RA (100 mg·kg −1 ). The pharmacokinetic profile of IL‐1RA was assessed in plasma and CSF up to 24 h post‐administration. Brain tissue distribution of administered IL‐1RA was assessed using immunohistochemistry. In a separate experiment, the neuroprotective effect of the single s.c. dose of IL‐1RA in MCAo was assessed versus a placebo control group. Key results: A single s.c. dose of IL‐1RA reduced damage caused by MCAo by 33%. This dose resulted in sustained, high concentrations in plasma and CSF, penetrated brain tissue exclusively in areas of blood–brain barrier breakdown and co‐localized with morphologically viable neurones. CSF concentrations did not reflect massive parenchymal infiltration of IL‐1RA in MCAo animals compared to naïve. Conclusions and implications: These data are the first to show that a potential treatment for stroke, IL‐1RA, rapidly reaches salvageable brain tissue via an administration route that is clinically relevant. This allows confidence that IL‐1RA, as a candidate for further clinical development, is able to confer its protective actions both peripherally and centrally." @default.
• W2132453743 created "2016-06-24" @default.
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• W2132453743 date "2010-04-13" @default.
• W2132453743 modified "2023-10-16" @default.
• W2132453743 title "Rapid brain penetration of interleukin-1 receptor antagonist in rat cerebral ischaemia: pharmacokinetics, distribution, protection" @default.
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• W2132453743 doi "https://doi.org/10.1111/j.1476-5381.2010.00684.x" @default.
• W2132453743 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2860215" @default.
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