Intranasal Administration of Interleukin-1 Receptor Antagonist in a Transient Focal Cerebral Ischemia Rat Model.
10.4062/biomolther.2016.050
- Author:
Jae Hoon LEE
1
;
Eun Hee KAM
;
Jeong Min KIM
;
So Yeon KIM
;
Eun Jeong KIM
;
So Yeong CHEON
;
Bon Nyeo KOO
Author Information
1. Department of Anesthesiology and Pain Medicine, Severance Hospital, Republic of Korea. koobn@yuhs.ac
- Publication Type:Original Article
- Keywords:
Cerebral ischemia;
Interleukin-1 receptor antagonist;
Intranasal administration;
Neuroinflammation
- MeSH:
Administration, Intranasal*;
Animals;
Blood-Brain Barrier;
Brain;
Brain Ischemia*;
Cytokines;
Humans;
Infarction, Middle Cerebral Artery;
Interleukin 1 Receptor Antagonist Protein;
Interleukin-1*;
Ischemic Attack, Transient;
Male;
Methods;
Microglia;
Models, Animal*;
Necrosis;
Neurons;
Neuroprotection;
Rats*;
Rats, Sprague-Dawley;
Stroke
- From:Biomolecules & Therapeutics
2017;25(2):149-157
- CountryRepublic of Korea
- Language:English
-
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.
