Journal article
The Role of κ Opioid Receptor in Brain Ischemia
Critical care medicine, Vol.44(12), pp.e1219-e1225
12/2016
DOI: 10.1097/CCM.0000000000001959
PMCID: PMC5203937
PMID: 27495821
Abstract
Our previous studies indicated that highly selective κ opioid receptor agonists could protect the brain, indicating an important role of κ opioid receptor agonist in brain ischemia. In this study, we investigated the role and related mechanisms of κ opioid receptor agonists in brain ischemia in a middle cerebral artery occlusion mouse model.
Animal model.
Laboratory.
The middle cerebral artery occlusion model was established by 120 minutes of ischemia followed by 24-hour reperfusion in male adult mice.
Various doses of salvinorin A, a highly selective and potent κ opioid receptor agonist, were administered intranasally 10 minutes after initiation of reperfusion. Norbinaltorphimine (2.5 mg/kg, IP) as a κ opioid receptor antagonist was administered in one group before administration of salvinorin A (50μg/kg) to investigate the specific role of κ opioid receptor.
Infarct volume, κ opioid receptor expression, and Evans blue extravasation in the brain, and neurobehavioral outcome were determined. Immunohistochemistry and western blot were performed to detect the activated caspase-3, interleukin-10, and tumor necrosis factor-α levels to investigate the role of apoptosis and inflammation. κ opioid receptor expression was elevated significantly in the ischemic penumbral area compared with that in the nonischemic area. Salvinorin A reduced infarct volume and improved neurologic deficits dose-dependently. Salvinorin A at the dose of 50 μg/kg reduced Evans blue extravasation, suggesting reduced impairment of the blood-brain barrier and decreased the expression of cleaved caspase-3, interleukin-10, and tumor necrosis factor-α in the penumbral areas. All these changes were blocked or alleviated by norbinaltorphimine.
κ opioid receptors were up-regulated and played a critical role in brain ischemia and reperfusion. κ opioid receptor activation could potentially protect the brain and improve neurologic outcome via blood-brain barrier protection, apoptosis reduction, and inflammation inhibition.
Details
- Title: Subtitle
- The Role of κ Opioid Receptor in Brain Ischemia
- Creators
- Chunhua Chen - 1Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.2Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.3Department of Anesthesiology, Renji Hospital, Jiaotong University School of Medicine, Shanghai, China.4Department of Biology, University of Pennsylvania, Philadelphia, PAChunhua XiXuan LiangJingyuan MaDiansan SuTed AbelRenyu Liu
- Resource Type
- Journal article
- Publication Details
- Critical care medicine, Vol.44(12), pp.e1219-e1225
- DOI
- 10.1097/CCM.0000000000001959
- PMID
- 27495821
- PMCID
- PMC5203937
- NLM abbreviation
- Crit Care Med
- ISSN
- 0090-3493
- eISSN
- 1530-0293
- Publisher
- United States
- Grant note
- R01 GM111421 / NIGMS NIH HHS K08 GM093115 / NIGMS NIH HHS
- Language
- English
- Date published
- 12/2016
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065738002771
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