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http://dx.doi.org/10.4062/biomolther.2016.050

Intranasal Administration of Interleukin-1 Receptor Antagonist in a Transient Focal Cerebral Ischemia Rat Model  

Lee, Jae Hoon (Department of Anesthesiology and Pain Medicine, Severance Hospital)
Kam, Eun Hee (Anesthesia and Pain Research Institute, Yonsei University College of Medicine)
Kim, Jeong Min (Department of Anesthesiology and Pain Medicine, Severance Hospital)
Kim, So Yeon (Department of Anesthesiology and Pain Medicine, Severance Hospital)
Kim, Eun Jeong (Department of Anesthesiology and Pain Medicine, Severance Hospital)
Cheon, So Yeong (Anesthesia and Pain Research Institute, Yonsei University College of Medicine)
Koo, Bon-Nyeo (Department of Anesthesiology and Pain Medicine, Severance Hospital)
Publication Information
Biomolecules & Therapeutics / v.25, no.2, 2017 , pp. 149-157 More about this Journal
Abstract
The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of $interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.
Keywords
Cerebral ischemia; Interleukin-1 receptor antagonist; Intranasal administration; Neuroinflammation;
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