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

Authors
 Jae Hoon Lee  ;  Eun Hee Kam  ;  Jeong Min Kim  ;  So Yeon Kim  ;  Eun Jeong Kim  ;  So Yeong Cheon  ;  Bon-Nyeo Koo 
Citation
 Biomolecules & Therapeutics, Vol.25(2) : 149-157, 2017 
Journal Title
 Biomolecules & Therapeutics 
ISSN
 1976-9148 
Issue Date
2017
Keywords
Cerebral ischemia ; Interleukin-1 receptor antagonist ; Intranasal administration ; Neuroinflammation
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-1β and tumor necrosis factor-α 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.
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DOI
10.4062/biomolther.2016.050
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
구본녀(Koo, Bon-Nyeo) ORCID logo https://orcid.org/0000-0002-3189-1673
김소연(Kim, So Yeon) ORCID logo https://orcid.org/0000-0001-5352-157X
김은정(Kim, Eun Jung) ORCID logo https://orcid.org/0000-0002-5693-1336
김정민(Kim, Jeongmin) ORCID logo https://orcid.org/0000-0002-0468-8012
이재훈(Lee, Jae Hoon) ORCID logo https://orcid.org/0000-0001-6679-2782
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154662
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