Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemiaopen access
- Authors
- Ullah, Irfan; Chung, Kunho; Oh, Jungju; Beloor, Jagadish; Bae, Sumin; Lee, Sangah Clara; Lee, Minhyung; Kumar, Priti; Lee, Sang-Kyung
- Issue Date
- Oct-2018
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v.8
- Indexed
- SCIE
SCOPUS
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 8
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4673
- DOI
- 10.1038/s41598-018-33296-z
- ISSN
- 2045-2322
- Abstract
- Ischemic stroke-induced neuronal cell death results in the permanent disabling of brain function. Apoptotic mechanisms are thought to play a prominent role in neuronal injury and ample evidence implicates Fas signaling in mediating cell death. In this study, we describe the neuroprotective effects of a Fas-blocking peptide (FBP) that by obstructing Fas signaling in cerebral ischemia inhibits apoptosis. Using an intranasal administration route in a rat model of focal cerebral ischemia, we demonstrate that nose-to-brain delivery of FBP after middle cerebral artery occlusion (MCAO) surgery results in the delivery and retention of FBP in Fas-expressing ischemic areas of the brain. A single intranasal administration of 2 mg/kg FBP resulted in significantly reduced neuronal cell death by inhibiting Fas-mediated apoptosis leading to decreased infarct volumes, reduced neurologic deficit scores and recovery from cerebral ischemia. Intranasally delivered FBP might be a promising strategy for the treatment of cerebral ischemic stroke.
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